Professional Documents
Culture Documents
IN
ORGANIC CHEMISTRY
BY
LOUIS F. FIESER
Sheldon Emery Professor of Organic Chemistry
Harvard University
SECOND EDITION
Louis F. FIESER
CAMBRIDGE, MASSACHUSETTS
April, 1935
I N CASE OF ACCIDENTS 7
PART I
EXPERIMENT
1. DETECTION OF THE ELEMENTS 9
2. DISTILLATION 14
3. FRACTIONAL DISTILLATION 19
4. DETERMINATION OF MKLTING POINTS 26
5. CRYSTALLIZATION 33
6. EXTRACTION 40
7. THE AMYLENES (2-METHYL-BUTENE-2 AND PENTENE-2) 46
8. REACTIONS OF THE SATURATED AND UNSATURATED HYDRO-
CARBONS 49
9. «-BUTYL BROMIDE 52
10. DlETHYL ETHKR 58
11. METHYL BENZOATE 62
12. TRIPHESYLCARBINOL (GRIGNARD SYNTHESIS) 67
13. BENZOIC ACID AND #-VALERIC ACID (CARBONATION OF THE
GRIGNARD REAGENT) 72
14. ACETYL CHLORIDE 76
15. ALDEHYDES 79
16. REACTIONS or ALDEHYDES AND KETONES. 84
17. ACETAMIDE 91
18. SYNTHESIS OF MANDELIC ACID 94
19. PINACOL HYDRATE 97
20. SUCCINIC ANHYDRIDE 103
21. CHARACTERIZATION OF THE AMINES 106
22. PHYSIOLOGICAL FORMATION or HIPPURIC ACID 113
23. UREA FROM URINE 117
24. SUGARS . . . -. 121
25. POLYSACCHARTDES 129
26. SODIUM /"-TOLUENE SULFONATE 136
27. SODIUM /3-NAPHTHALENE SULFONATE 142
28. NITROBENZENE , 144
vii
viii CONTENTS
EXPERIMENT PAGE
29. ANILINE 147
STEAM DISTILLATION 153
30. ACETANILIDE 163
31. ^-BROHOACETAFTCLIKE . 167
32. />-NlTROACETANILIDE 170
33. /S-NAPHTIIOL 171
34. DlPIIENYLMETIIANE (FRIEDEL AND CRAFTS HYDROCARBON
SYNTHESIS) 175
35. tert.-BVTVLBENZENE AND />-to-/.-BUTYLPHENOL 179
36. O-BENZOYLBENZOIC ACID 183
37. ANTHRAQUINONE 189
38. I-BENZOYLNAPHTIIALENE. 192
39. BENZOPHENONE 197
40. BEXZOPINACOL 202
41. Azo DYES 206
42. O-CHLOROTOLUENE. 213
43. BENZOIC ACID AND FHENYLGLYOXYLIC ACID 217
44. ACETYLSALICYLIC ACID 222
45. BENZOIN AND BENZIL 224
46. QUINONES 228
VACUUM DISTILLATION 240
47. NAPHTHOL-AS (ANILIDE OF 2-HYDROXY-3-NAPHTHOIC ACID) . . 254
48. DYES AND DYEING 257
49. SULFANTLAMIDE 262
50. ABIETIC ACID 265
51. T H E IDENTIFICATION OF ORGANIC COMPOUNDS 268
52. MAETIUS YELLOW AND ITS REDUCTION PRODUCTS 278
PART II
CHAPTER I
SUGGESTIONS FOR ADVANCED WORK 291
Trial Runs • Notebooks • Reporting Yields
Use of the Literature • Literature Searches • Reference Works
Benzene-Ring Stamps
Purification of a Sample for Analysis • Vacuum Sublimation • Dry-
ing Pistol • Blocks for Mailing Samples
CHAPTER II
APPARATUS AND METHODS 303
Equipment for the Laboratory Bench • Acid Bath • Heating Baths •
Cooling Baths • Stirring Motor • Stirring • Stirrer Seals • Addi-
CONTENTS IX
PAGE
tion Tubes • Gas Traps • Pressure Reactions • Ultraviolet Lamp •
Distillation • Manometers • Steam Distillation • Filtration • Evap-
oration of Solvent • Polarizing Microscope
Determination of Melting Points • Melting Point Tube • Precision
Apparatus • Melting Point Blocks • Microdetermination of Melt-
ing Points
Manipulation of Small Quantities of Material • Small Suction Filters •
Microburner • Filter Sticks • Centrifuge Tube Technique • Centri-
fuge Filtration
Chromatographic Adsorption • Separation of Plant Pigments • General
Uses of the Tswett Column • Columns for Suction and Pressure
Filtration • Activated Alumina • Magnesium Sulfate • Purification
with an Adsorption Column • Recovery of Hydrocarbons from
Picrates • Method of Fractional Elution • Experiments
Glass Blowing (By E. B. Hershberg) • Types of Glass • Cutting Glass
Tubing • Flaring of Glass Tubing • Bends • Round Ends • Straight
Seals • T-Seals • Bulbs • Ring Seals • Rings • Use of Asbestos •
Glass Grinding • Chipping a Rough Surface
CHAPTER III
SOLVENTS, REAGENTS, AND GASES 357
Solvents • Absolute Alcohol • Methyl Alcohol • Absolute Ether • Ace-
tone • Benzene • Toluene • Ethyl Acetate • Ligroin and Petroleum
Ether • Carbon Bisulfide • Carbon Tetrachloride • Chloroform •
Methylene Chloride • Ethylene Chloride • .s-Tetrachloroethane •
Chlorobenzene and Other Aromatic Chlorides • Nitrobenzene •
Pyridine • Quinoline Substitute • Dioxane • Cellosolve and Carbitol
Solvents
Drying Agents • Calcium Chloride • Potassium Hydroxide • Sodium •
Phosphorus Pentoxide • Potassium Carbonate • Neutral Anhy-
drous Salts • Absorbent Cotton
Alkylating Agents • Alkyl Iodides • Alkyl Bromides • tefJ.-Butyl
Chloride • Alkyl Sulfates • Alkyl ^-Toluene Sulfonates • Diazo-
methane
Acylating Agents • Acetic Anhydride • Acetyl Chloride • Benzoyl
Chloride • Benzenesulfonyl Chloride • />-Toluenesulfonyl Chlo-
ride • Other Acid Chlorides
Other Reagents • Thionyl Chloride • Ethyl Formate • Dimethyl-
aniline • Aniline • Ethylene Oxide • Acetylene • Aldehydes • 2,3-
Dimethylbutadiene-1,3 • Piperylene and Butadiene • Sodium
Ethoxide • Sodium Ethoxide Solution • Fused Sodium Acetate •
X CONTENTS
PAGE
Hydrogen Cyanide • Liquid Hydrogen Fluoride • Cyanogen Bro-
mide • Iodine Monobromide • Boron Fluoride • Sodium Aluminum
Chloride
Inorganic Gases • Ammonia • Carbon Dioxide • Carbon Monoxide •
Chlorine • Hydrogen Bromide • Hydrogen Chloride • Nitrogen •
Sulfur Dioxide • Nitric Oxide
CHAPTER IV
REACTIONS , 397
Acylation • Catalysts • Acetylation in Aqueous Solution • Schotten-
Baumann Method • Kaufmann's Procedure • Reductive Acetyla-
tion • Acetylation with Ketene • Formylation • Carbobenzoxyla-
tion • Acylation of Tertiary Alcohols
The Grignard Reaction • Apparatus • Starting the Reaction • Analysis
and Detection of the Reagent • The Reaction Proper • Hydrolysis
of the Reaction Mixture • Lithium Derivatives • Manipulation of
Lithium
The Friedel and Crafts Reaction • Hydrocarbon Synthesis • Synthesis
of Ketones and Keto Acids • Influence of Solvents • Use of Stannic
Chloride • Cyclization Procedures
Reduction • Miscellaneous Reducing Agents • The Clemmensen
Method • The Wolff-Kishner Method • Reduction with Aluminum
Alkoxides • Hydrogen Iodide and Red Phosphorus
Oxidation • Miscellaneous Oxidizing Agents • Hydrogen Peroxide •
Peracids • Selenium Dioxide • Lead Tetraacetate • Periodic Acid •
Silver Benzoate-Iodine • Osmium Tetroxide • Caro's Acid • Potas-
sium Persulfate • Oppenauer Oxidation
Catalytic Hydrogenalion • Hydrogenation Flasks • Preparation of
Noble Metal Catalysts • Specific Uses of Platinum and Palladium •
Factors Favoring Hydrogenation • Promoters • High-pressure
Hydrogenation • Raney Nickel
Dehydrogenation • Sulfur • Selenium • Preparation of Platinum and
Palladium Catalysts • Liquid Phase Catalytic Dehydrogenations •
Effect of Boiling • Apparatus • Other Methods
CHAPTER V
T H E SEMIMICRODETERMINATION OF CARBON AND HYDROGEN 465
INDEX 475
EXPERIMENTS IN
ORGANIC CHEMISTRY
SECOND EDITION
EXPERIMENTS IN ORGANIC CHEMISTRY
INTRODUCTION
Instruction in the laboratory methods of organic chemistry
has a purpose beyond the obvious one of providing practical
training essential to the prospective chemist. In affording an
opportunity for the student to become acquainted with a num-
ber of representative organic compounds, to observe their special
properties and characteristic behaviors, and to have some ex-
perience with the methods of handling them, such work forms a
supplement to a lecture course which is essential to a full under-
standing and appreciation of the subject. With thought and
study much information regarding the general theory of the
carbon compounds can be gained in the organic laboratory, and
there is in addition ample opportunity for acquiring manipula-
tive skill and dexterity. Organic compounds present such an
interesting array of properties and reactions, and the methods
of manipulation are so ingenious, that work in the organic
laboratory is usually found to be a stimulating experience.
For those who become particularly interested and who develop
suitable proficiency there is a wide field even in an elementary
course for special experimentation.
The Nature of the Experiments. — Most of the laboratory
operations of organic chemistry have to do with the preparation,
the purification, or the characterization of compounds and there
is some grouping of the experiments given below according to
this classification. The first few sections deal largely with the
common methods of purifying organic substances, and the prepa-
rations which follow require constant use of these methods in the
separation of the reaction product from the by-products and
tars almost invariably formed in the course of the reaction.
2 INTRODUCTION
The samples prepared and purified are all to be tested for purity,
and this is an important part of the characterization; they are
also used in making practice tests of the reactions and properties
characteristic of the types of which the substances are repre-
sentatives. This matter of testing is given further emphasis in
special chapters, and toward the end of the book the problem is
presented of identifying certain substances by the application of
the various tests studied.
Precautions. — Work in the organic laboratory is attended
with certain special hazards, the chief of which is that from fire,
for nearly all of the liquid chemicals and the solvents are highly
inflammable substances, and the use of a free flame cannot be
avoided in a great many of the common operations. Fortu-
nately, however, methods have been developed for handling the
inflammable materials with almost complete safety, and the
realization of the danger should not be a source of alarm but
rather a cause for the utmost caution. The warnings and pre-
cautions given in this book and further supplemented by such
special laboratory rules as may be issued by the instructor must
be followed explicitly. There is further danger of injury in the
handling of acids, alkalies, metallic sodium, and bromine, and in
working with such extremely poisonous substances as potassium
cyanide; but the careful and thoughtful worker who heeds all
advice and instructions given can perform experiments with
such substances with equanimity.
In order to be prepared for an accident to yourself or to others,
familiarize yourself with the safety devices and first-aid supplies
of your laboratory, and read the instructions given on page 7.
In addition to recognizing the possibility of injury to the per-
son it must be borne in mind that considerable care has to be
exercised to avoid damage to the clothing and to the laboratory.
Perhaps the chief source of difficulty is in the use of concen-
trated sulfuric acid, for the acid almost invariably drips when
poured from a reagent bottle and its destructive action on wood,
wool, cotton, and other materials is extremely rapid. Remem-
ber this and always pour the reagent over a sink when possible
INTRODUCTION 3
and always look for any drippings on the side of the bottle or
elsewhere and wash immediately with plenty of water. Reagent
bottles and flasks containing sulfuric acid must be put away in
the desk in such a way that there is no possibility of their spilling.
Solutions of alkalies are particularly destructive to wool and to
the skin and they must be handled with the same care.
It is hardly necessary to point out that, quite apart from con-
siderations of safety and protection, neat and careful manipu-
lation is a mark of good technique. With a wet and a dry towel
always handy, desks can be kept spotlessly clean. By washing
vessels as soon as they have been used, or at least shortly after-
wards, a supply of clean apparatus can be assured. Incidentally,
tars and dirt are always most easily removed when they are
fresh and while one still remembers the nature of the material
and hence can judge of the best loosening agent. It is obvious
that solid waste and papers must not be thrown into the sink.
It is clear further that in handling noxious gases or vapors con-
sideration for one's neighbors if not for one's self demands the
use of a hood or of a suitable confining device.
Bending glass and boring corks. — The experiences gained
in elementary courses should not be forgotten. A wash bottle
should be constructed at the beginning of the course and used
whenever an opportunity presents itself. Glass tubing can be
cut cleanly by making a short but distinct file mark, placing the
thumbs together on the side opposite the cut, and exerting a
slight pressure. Bends are made most easily by heating the
glass in the smoky flame of a burner provided with a wing top.
The ends of glass tubes and stirring rods always should be fire
polished.
There are several points to be remembered in selecting and
boring a cork stopper. A cork used in contact with a hot liquid,
as when it supports a thermometer in a distilling flask, becomes
considerably softened and it may have to be pushed in further
in order to make a tight fit. It is thus advisable to select a cork
which originally fits only a short distance into the flask and which
may even seem to be too large. Before being bored it is softened
4 INTRODUCTION
between the rubber and the glass, and working it around the cir-
cumference of the tube; the other end is loosened in the same way.
Amounts of reagents are often of great importance and wher-
ever an exact amount is specified this is to be weighed or meas-
ured as accurately as the apparatus available permits. Even
when the quantity does not have to be exact it is important to
keep within reasonable limits both to insure the success of the
operation and to avoid needless waste. Where the directions
call for the use, for example, of 3-5 cc. of a liquid the figures
should be taken to indicate the upper and lower limits and one
should aim to adhere to the specifications. A convenient
approximate measure of 1 cc. is given by a 2 cm. column of
liquid in an I I X 75 mm. test tube. It is well at the start to
measure all volumes accurately in order to gain experience
sufficient for making reliable estimations. It is much more
difficult to guess weights on account of the great differences in
the density and the state of compactness of common materials.
Thus the approximate volumes occupied by one gram each of
crystalline iodoform (CHI3), animal charcoal, and crystalline
benzoic acid (C6H5COOH) are 1 cc, 7 cc, and 12 cc, respectively.
Reliable estimates can only be made after practice weighings,
and it is particularly important to do this in the case of animal
charcoal. An 11 X 75 mm. test tube holds approximately
0.5 g. of charcoal when lightly packed.
Preparation for laboratory work. — In order to work effi-
ciently it is quite essential to study the experiments in advance
and to lay definite plans for the utilization of the time available.
Certain operations, such as the heating of a reaction mixture,
often require definite, stated periods of time and it is obviously
necessary to arrange for this. It often happens that there are
periods in an experiment during which the operator's full atten-
tion is not required, and the intelligent worker makes good use
of these periods by working on other experiments, cleaning
apparatus, obtaining supplies for future operations or otherwise
busying himself.
It is an excellent plan to make some entries in the notebook
6 INTRODUCTION
the tube is still hot, and with the asbestos still attached to serve
as a guard, drop the tube with care into a small beaker contain-
ing 10-15 cc - °f distilled water. The tube should crack and the
sodium will then react violently with the water. Crush the
glass and the charred material, boil for a few minutes, and
filter. Save a part of the solution for the sulfur test below.
(In case the sample is to be tested also for halogen proceed as
described on page 11.)
To a portion of the solution add 5-6 drops of ferrous sulfate
solution, 2 drops of ferric chloride solution, and 1-2 cc. of dilute
sodium hydroxide solution. Make sure that it is alkaline by
testing with litmus and then boil for a minute or two. Ferrous
and ferric hydroxides precipitate and sodium ferrocyanide is
formed. Now cool and acidify with dilute sulfuric acid. The
brown precipitate dissolves, the ferric chloride reacts with the
ferrocyanide to produce Prussian blue, which appears as a fine
blue precipitate. If the amount of nitrogen in the sample is
very small, or if in fusing much of the material volatilized before
it reacted, no precipitate may be visible at first and one obtains
only a greenish-blue solution. If this is shaken well and allowed
to stand for a time, the precipitate may become perceptible,
particularly if the solution is filtered and the paper examined
carefully. In case of failure repeat the fusion, being careful to
have the sodium hot enough so that its vapor begins to rise in
the tube at the moment the sample is added.
Sulfur: (A) Sodium Fusion. — The fusion of a sulfur com-
pound with sodium gives sodium sulfide. This may be detected
by the violet or brown coloration produced by adding sodium
nitroprusside, Na2Fe(CN)sN0 (equation not known definitely),
or by the precipitation of lead sulfide from a solution of sodium
plumbite. The latter test is the more sensitive.
Experiment: To a portion of the alkaline solution obtained
from the sodium fusion of the sample (see under " Nitrogen ")
add a drop or two of sodium nitroprusside solution and see if there
is a deep coloration. For the second test, prepare a solution of
sodium plumbite by adding dilute sodium hydroxide solution to
DETECTION OF THE ELEMENTS 13
about 0.5 cc. of 0.1 M lead acetate solution until the initial
precipitate just redissolves, and add a portion of the alkaline
solution under investigation. A black precipitate or a colloidal
brown suspension indicates the presence of sulfur. Freshly pre-
pared sodium plumbite solution should be used.
(B) The Carius Test. — The principle involved here is to
destroy the organic compound by oxidation with nitric acid,
the sulfur being converted into sulfuric acid, which is easily
identified. It is a convenient method in those cases where it is
easily applicable, but many sulfur compounds are decomposed
by nitric acid only when heated with this reagent in a sealed
tube at 250-3000.
Experiment: Cover a small spatulaful of sulfanilic acid with
3 cc. of concentrated nitric acid in a large Pyrex test tube and
warm the mixture carefully until the rather vigorous reaction
begins and then heat more strongly. When no further reaction
occurs on heating, pour in distilled water until the tube is about
half-filled, and add 3 cc. of 5 per cent barium nitrate solution.
A white precipitate of barium sulfate indicates the presence of
sulfur.
EXPERIMENT 2
DISTILLATION
This operation is of great use in the organic laboratory for
the purification of volatile compounds and in judging the purity
of such substances. Traces of colored impurities which are
either non-volatile or slightly volatile are easily eliminated in
this way. It frequently happens in the preparation of an organic
liquid that the product is accompanied by small amounts of
materials some of which are more volatile, some less volatile
than the substance itself. Hence in carrying out the distilla-
tion the first portion or fraction of the distillate is collected
separately (" fore-run ") and discarded, and as the boiling point
rises close to the true boiling point of the desired product the
receiver is changed and the main fraction is collected until the
liquid has nearly all distilled or until a further appreciable rise
in the boiling point indicates that the less volatile " after-run "
is beginning to come over.
A pure liquid boils very constantly at a definite point which
is defined as the temperature at which the vapor pressure of
the liquid is just equal to the atmospheric pressure. A change
in the boiling point during the progress of a distillation is a
definite indication that the liquid is not pure (or that it is a
mixture of two or more components which may be individually
"pure")- The converse proposition, however, is not always
true, and it is not always safe to conclude from the constancy of a
boiling point that the liquid is a pure individual. Thus if two
miscible liquids of similar structural type boil at exactly the same
temperature a mixture of the two will also boil at or very near
that temperature. Furthermore, some liquids form constant-
boiling mixtures, that is, mixtures which will distil completely
without any change in the boiling point or in the composition of
14
DISTILLATION 15
tube, and in the center. Fill the flask about one-half full with
distilled water, add a small piece of porous plate to prevent
bumping, and distil as long as is necessary to establish with
certainty the boiling point. The flask may be heated rather
rapidly until boiling begins; the flame should then be decreased
and adjusted so that the distillate drops at a regular rate (about
one drop per second). Remember that it takes an appreciable
time at the beginning for the vapor to heat thoroughly the upper
part of the flask and the thermometer. It is a mistake to distil
too slowly, for the thermometer may then momentarily cool
from lack of sufncie.nt contact with fresh vapor. On the other
hand, the flame used should not be so large that it heats directly
a part of the vapor rather than just the liquid. This superheat-
ing is particularly likely to occur at the end of a distillation when
DISTILLATION 17
60
Composition
FIG. 4. — Distillation Curves
its more volatile part; the less volatile constituents of the vapor
are condensed, dropping back into the flask. Similar partial
condensation of the vapor (and partial volatilization of the
condensate) occurs at several different levels of the column and
it will be seen that the column effects what amounts to several
separate distillations. The liquid which continually drops back
into the flask from the column corresponds to a fraction which,
in an ordinary distillation, would be collected from the condenser
and put back in the flask by hand for a subsequent distillation.
In order to appreciate fully the theory of fractional distillation
it is necessary to consider distillation curves such as those given
in Fig. 4 for mixtures of acetone and toluene. The composition
is plotted on the abscissa: the concentration of toluene varies
from 100 per cent at the left to zero per cent at the right of the
22 EXPERIMENT 3
chart, while that of the acetone increases from zero per cent at
the left to 100 per cent at the extreme right. The mixture at
the mid-point contains equal parts by weight of the two com-
ponents. The lower curve marked " liquid " is drawn through
the boiling points of liquid mixtures of various compositions;
more strictly speaking, these " boiling points " are the tempera-
tures at which the mixtures begin to boil. Thus pure (ioo per
cent) toluene boils at 110.6°, pure acetone boils at 56.5°, and the
50 : 50 mixture begins to boil at 65.50. In the last case the
boiling point increases along the liquid curve to the left as dis-
tillation progresses and the liquid remaining becomes richer in
toluene and poorer in the more volatile acetone. It should be
noted that this curve was determined experimentally and that it
applies only to the particular pair of liquids under discussion.
For other pairs the curves may be of different shape or character.
The upper vapor curve now requires explanation. It gives
for each mixture of acetone and toluene the temperature at
which the vapor begins to condense. If the 50 per cent liquid
mixture is heated it starts to boil at 65.50, but if it is completely
vaporized and allowed to cool the first condensation of the vapor
occurs at a temperature of 86°, corresponding to the intersection
of the 50 per cent vertical with the vapor curve. The last of
the vapor will of course condense when the temperature drops
to 65.50. It is only with pure toluene or pure acetone that the
boiling point of the liquid is the same as the condensing tempera-
ture of the vapor and hence the curves come together only at
the two ends of the chart. The vapor curve like the liquid
curve is derived from experimental observations.
The course of a fractionation may now be followed with refer-
ence to the chart. Suppose that a solution of 20 parts of acetone
and 80 parts of toluene is distilled, and suppose for the sake of
simplicity that a large volume of the mixture is used and that
only a very small proportion of the total is collected in the first
fraction. The chart shows that this fraction will boil at 77.5°,
and a parallel line constructed at this temperature intersects the
vapor curve at a point corresponding to 66.5 per cent of acetone,
FRACTIONAL DISTILLATION 23
TABLE II
FRACTIONATIOK WITHOUT A COLUMN
into the flask 120 cc. of the prepared mixture of equal volumes
of carbon tetrachloride (b.p. 770, sp. gr. 1.58) and toluene
(b.p. 110.60, sp. gr. 0.866). Add a chip of porous plate and distil
carefully at a regular rate, and in such a manner that there is a
steady flow of condensate dropping back from the condenser.
Collect the portion which distils up to 82° in a 50-cc. or 125-cc.
Erlenmeyer flask labelled " I, to 82 0 ." When this temperature
is reached change the receiving flask and collect the next portion
in another clean flask marked " II, 82-93 0 ." When the boiling
point reaches 93° change to a third flask, " III, 93-1040," and
finally use a fourth flask, " IV, 104-111° " for the fraction boiling
in the range indicated. Allow the apparatus to cool somewhat,
so that the vapor in the flask and the column condenses. Pour
this condensate into a flask marked " V, Residue," and drain the
distilling flask well. This completes the first distillation; the
volumes of the various fractions are to be measured and recorded
in a table similar to Table II.
In beginning the second distillation pour the liquid in flask
I into the round-bottomed flask, distil and collect the portion
boiling up to 82° in flask I. When the boiling point reaches 82°
remove the flame, allow the flask to cool slightly and pour into
it the contents of II. Again distil, collecting the part boiling
FRACTIONAL DISTILLATION 25
FIG. 6. — Silver Spatula (top and side view) Made from No. 8 Coin Silver
Wire, Length 18 cm.
or cinnamic acid (m.p. 133°) and see how well you can check the
figures given (1-2° is satisfactory).
(2) Determine the melting point of either unknown X,
unknown Y, or unknown Z (they all melt close to 1300).
(3) By carrying out mixed melting point determinations see
if the unknown selected is identical with either urea or cinnamic
acid.
(4) Construct a rough chart showing the melting points of
mixtures of urea and cinnamic acid of approximately the fol-
lowing compositions:
UREA CINNAMIC ACID M.P. (MID-POINT or RANGE)
100% 0% 1330
80% 20% 1
(« 0, 1 Prepare these mixtures and
of a /w I determine each m.p.
20% 80% J
0% 100% 1330
member of the pair than in the other. Thus the substance may
be so soluble in alcohol that it will dissolve but will not crystal-
lize, while in water it is practically insoluble. Neither solvent
by itself would be of any value, but by using a suitable mixture
of the two one may have available a solvent having just the right
dissolving power to permit satisfactory crystallization. The
way to prepare such a mixture is to dissolve the substance in alco-
hol and add water at the boiling point drop by drop. Each
drop produces a cloudiness which at first quickly clears. When
the solution just fails to clear on shaking, a few drops of alcohol
are added to effect this result and the solution is now saturated
at the boiling point and should be in just the right condition for
crystallization.
Selection of Solvent. — The bes£ way of selecting a solvent
for the crystallization of a given compound is to carry out simple
solubility tests with a few of the common solvents. If the
substance dissolves easily in a cold solvent this medium obviously
would be unsuitable by itself, but it may be useful to observe
before discarding the solution if a second solvent with which the
first forms a " pair " will cause the solid to precipitate. If the
substance fails to dissolve in a cold solvent, the latter should
then be heated to boiling. If dissolution now occurs one should
cool the solution under the tap and if necessary rub the walls with
a stirring rod to be sure that it will separate on cooling. By
reheating and allowing the test solution to cool slowly, one can
see if well-formed crystals are obtainable.
In making such tests it is economical of both time and ma-
terials to use small test tubes ( n X 75 mm.). A convenient
stand may be made by boring holes in a small block of wood.
A very small pinch of the sample and about a quarter-inch column
of solvent are all that are required. The solid particles should be
broken by crushing them against the walls with a rounded stirring
rod. For adding the small amounts of liquids required it is con-
venient to use a dropping tube. This is just a section of glass
tubing about 23 cm. long and drawn down to a delivery tip at
one end; three or four of them should be kept on hand for
CRYSTALLIZATION 37
Filter paper
Witt plate
until you are convinced of the general truth of the rule that
" like dissolves like." From these and further solubility tests,
suggest a good solvent or solvent-pair with which to purify each
of the first three compounds.
(2) Decolorizalion of a Solution. — Crude phthalic acid,
C6H4(COOH)2, is to be crystallized, with the aid of animal
charcoal,1 until a colorless sample is obtained. Dissolve 2 g. of
the crude material in slightly more than the minimum quantity
of water in a 50-cc. Erlenmeyer flask, add a small spatulaful of
animal charcoal, boil for a few minutes, and filter the hot solution.
(3) Purification, and Testing for Purity. — Take the melting
point of a crude sample of ^-nitroaniline. Crystallize 5 g. of the
material until you believe it to be pure. Give your evidence for
this belief. Record the weight of pure product and turn it in
to the assistant.
1
The special decolorizing carbons known as Norit and Darco are particularly
effective.
EXPERIMENT 6
EXTRACTION
should be clasped in such a way that both the stopper and the
stopcock are held in place. The pressure is released not by
removing the stopper, but by inverting the funnel and carefully
turning the stopcock. As the evolution of carbon dioxide be-
comes less pronounced shake more vigorously, and when there
is little further reaction let the layers separate, loosen the stopper,
and carefully draw off the aqueous solution (lower layer) into
a 125-cc. Erlenmeyer flask. A further small volume of this
solution usually drains from the walls, particularly if the funnel
is given a rotary twist, and this should be collected. Extract
again with a 30 cc. portion of sodium bicarbonate solution and
combine this extract with the first one.
Pour the ethereal solution into a dry 125-cc. Erlenmeyer flask
from the mouth of the funnel (it would be contaminated with
water if run out of the stem), and rinse the funnel with a little
ether. Add 2-3 g. of anhydrous sodium sulfate and set the solu-
tion aside to dry while working up the other product.
The aqueous solution of sodium benzoate contains also a
certain amount of dissolved ether which carries along with it
some triphenylcarbinol. Heat the solution on the steam bath
for a few minutes until most of the ether has been driven off.
Now cool the solution well and filter it by gravity from any
material which separates and which is to be discarded, and acidify
the solution with dilute hydrochloric acid. It is well to carry
out this operation in a beaker and to add the acid slowly and
with stirring, for there is considerable foaming due to the libera-
tion of carbon dioxide from the excess carbonate. Collect the
solid which precipitates, wash it with water, dry and weigh it.
The ethereal solution is now filtered into a second Erlenmeyer
flask, using a little ether to rinse the flask and to wash the
material on the filter paper. To distil the ether add a chip
of porous plate (very necessary when boiling ether), place the
flask on the steam bath, and connect it by means of a bent glass
tube to a condenser arranged for downward distillation. Use
for the receiver a filter flask connected by means of an adapter.
This gives a closed system except for the side arm of the receiv-
EXTRACTION 45
ing flask. To prevent ether vapor from escaping here and catch-
ing fire, a rubber tube is attached and arranged to conduct the
vapor to the floor. Distil the ether completely and scrape out
the solid residue and let it dry. Record the weight.
Determine now the melting point, first of the original mix-
ture and then of each of the products of the extraction, and from
the results and from the weights you will be able to judge of the
success of your separation. After completing the remaining
part of the experiment, place the two samples in the containers
provided.
Consider now for comparison the possibility of separating the
original mixture by fractional crystallization. Make solubility
tests with the two samples isolated above as well as with a fresh
portion of the original mixture, and see if by crystallization you
can isolate either one or the other component, or possibly both of
them in a pure condition (use 4 g.). If you find the proper sol-
vent it should not be difficult to obtain one of the substances in a
reasonably pure condition; but you will probably be unable to
isolate more than one component in the time available. Com-
pare the advantages and disadvantages of the two methods of
separation.
EXPERIMENT 7
THE AMYLENES (2-Methyl-Butene-2 and Pentene-2)
Amylene is a general name for the rive isomeric ethylenic
hydrocarbons of the formula C5HI0. Two of them are readily
available through the dehydration of appropriate amyl alcohols
as follows:
CHj CIIj
QUESTIONS
1. From what other amyl alcohols could each of the above amylenes
be obtained by dehydration?
2. If perfectly pure pentene-2 is desired, which amyl alcohol would
you suggest as the best starting material?
3. Which of the following alcohols would be expected to undergo
dehydration "very easily," "easily," or not at all: CH3CH2CH2OH,
(CH3)2CHOH, (CH3)3CCH2OH?
EXPERIMENT 8
REACTIONS OF THE SATURATED AND
UNSATURATED HYDROCARBONS
Mor.KS
REAGENTS \MOUNT Si>. GR. B.P.
ACTUAL TlIEORKT.
XaBr. 65g- 0 63 O 50
H.SO4 94 •5° 1 84
CJIjOH 37 g- •5° •5° 0 810
PRODUCT: CII3CH2CH2CH2Br
WEIGHT B.P.
MOL.
% YIELD SP. GK.
WEIGHT
THEORET. ACTUAL GIVEN FOUND
it is seen that for one mole of butyl alcohol there is required one
mole of sodium bromide and one mole of sulfuric acid. In
54 EXPERIMENT 9
QUESTIONS
1. What experimental method would you recommend for the
preparation of »-octyl bromide? fer/.-Butyl bromide?
1
The simplest method of telling layers apart is to see which one will mix with
water. In the present case one can draw off a few drops of the lower layer into a
test tube of water; butyl bromide will not dissolve, sulfuric acid will do so.
»-BUTYL BROMIDE 57
Fig. 10. A thermometer is fitted into one hole of the cork stopper
and adjusted so that the bulb will be completely immersed when
the flask is about one-third filled with liquid, for it is the tem-
perature of the reaction mixture and not that of the vapor which
requires controlling. Through the other hole is inserted the
stem of a separatory funnel which is to be used for introduc-
ing the alcohol underneath the surface of the ethyl sulfuric
acid in the flask. (If the alcohol were simply dropped in
it would not mix well and it would largely volatilize before
having a chance to react.) The stem of the funnel is seldom
long enough to reach to the bottom of the flask and so it is
pieced out by means of a length of glass tubing attached to it
with a short rubber tube (push the two glass ends as close
together as possible). It is convenient to draw out the lower
end of this tube slightly and bend it upwards in the manner
shown, for this gives a better flow of alcohol. Make sure that
the stopcock of the separatory funnel fits tightly and that it is
properly greased. In turning the stopcock be careful never to
loosen it; exert a slight pressure inwards, so as to tighten it.
These precautions are very necessary for alcohol might other-
wise leak out and take fire.
The distillate is to be collected in a filter flask or distilling
flask connected to the end of the condenser by means of an
adapter and cooled in a slush of ice and water to minimize
volatilization losses. Even with good cooling enough ether
vapor will escape to present a fire hazard unless the vapor is led
off to the floor through a rubber tube attached to the side arm
of the receiver.
Pour 50 cc. of alcohol (95 per cent by volume) into the flask
and add cautiously and with good shaking 50 cc. of concentrated
sulfuric acid. Heat the mixture on an asbestos wire gauze
until the thermometer records a temperature of 1400, measure
100 cc. of alcohol and pour it into the separatory funnel (remove
the flame while pouring!). Now turn the stopcock carefully
and allow a slow stream of alcohol vapor to bubble up through
the liquid in the flask. The temperature must be kept between
METHYL ETHER 6I
and boil the mixture gently until all the oil has disappeared
(about 30 minutes). Disconnect the apparatus, cool the solu-
tion and make sure that the water-insoluble ester has been com-
pletely consumed, and acidify with dilute hydrochloric acid.
The separation of the solid (benzoic acid), coupled with the
fact that it was before in solution in the alkali (as sodium
benzoate), shows that the reaction leads to the formation of an
acid.
Optional. — Boil a piece of tallow about the size of a pea with
alkali in the manner described above, and determine if this
substance has the properties of an ester.
ALTERNATE PREPARATIONS
Methyl Salicylate (Oil of Wintergreen). — This is prepared
by the esterification of salicylic acid, a hydroxyl derivative of
benzoic acid having the formula CcH^OHQCOOH. The hy-
droxyl group is close in space to the carboxyl group and it tends
to ward off the esterifying alcohol and so to slow down the
reaction. In order to prepare this fragrant ester in good yield,
use 0.2 mole of salicylic acid and follow in other details the
procedure given above with the one exception that the refluxing
with alcohol and sulfuric acid should be continued for at least
5 hours. Even then there may be some unesterified acid and
this should be completely removed with sodium bicarbonate.
The ethereal solution is in this case best dried with anhydrous
magnesium sulfate (see Note 2, page 63). The pure ester boils at
2220, corr.; the yield is 75-80 per cent of the theoretical amount.
Methyl ortho-Benzoyl Benzoate. — This preparation calls for
somewhat more skill and care than the other esterifications
because the product is a low-melting solid which crystallizes a
little slowly and which can be purified by distillation only at
diminished pressure, for at the high temperature of atmospheric
distillation it undergoes decomposition. The acid concerned is
ortho-benzoylbenzoic acid, CeHsCOCeBuCOOH, and its prepara-
tion and properties are described in a later experiment. All
66 EXPERIMENT Jl
(Grignard Synthesis)
The synthesis of a tertiary alcohol usually is accomplished
by allowing'a suitable Grignard reagent to react with either an
ester or a ketone. An acid chloride may also be used as the
carbonyl compound, but it reacts so vigorously that the process
is not easily controlled. For the preparation of triphenylcar-
binol, (C6H6)3COH, it is thus convenient to employ either an
ester of benzoic acid, C6H6COOR, or benzophenone, (C6H5)2CO.
Each of these compounds reacts smoothly with phenyl magne-
sium bromide, C6H5MgBr, to give the desired alcohol; but since
the ester is only half as expensive as the ketone it is the preferred
reagent.
The first part of the preparation, namely the formation of the
Grignard reagent from bromobenzene, C6H5Br, magnesium and
ether, is the most difficult part of the process and it is neces-
sary to follow the directions carefully, particularly in the matter
of using dry reagents and dry apparatus, in order to meet with
success. The subsequent reaction proceeds well with either
methyl or ethyl benzoate. When the methyl ester is used, an
intermediate addition product separates as a white solid; the
intermediate formed on reaction with ethyl benzoate is more
soluble in ether and remains in solution.
The final magnesium compound, (C6H5)8COMgBr, is decom-
posed by treating it with water containing sufficient sulfuric acid
to dissolve the basic magnesium bromide, Mg(OH)Br, and the
triphenylcarbinol is extracted, along with the organic impuri-
ties, with ether. The chief impurity, other than unreacted
reagents, is the substance diphenyl (CeHU.CeEU) which is in-
67
68 EXPERIMENT 12
Steam
Inlet
27.2 cc. (34.8 g.) of pure w"-butyl bromide and a total of 85 cc.
of ether. After drying the flask containing the magnesium
pour in 5 cc. of the w-butyl bromide and 10 cc. of ether and
start the reaction by pressing the metal against the bottom with
a stirring rod. Once the reaction has commenced, run in a mix-
ture of the remaining 22.2 cc. of the halide and 75 cc. of ether
in the course of about 30 minutes and while warming the reaction
flask very gently on the steam bath. After refluxing for about
one hour longer the reaction should be practically complete.
Disconnect the flask and slowly decant the solution from any
unchanged magnesium gnto 60 g. (rough weight) of dry ice
contained in a dry 600-oc. beaker (see the footnote on page 73).
The vigorous boiling soon subsides and there is formed a stiff
glass of the MgBr-salt. When the dry ice has evaporated add
150 g. of ordinary ice and 30 cc. of concentrated hydrochloric
acid. Stir until there is a clean separation into two layers and
pour the mixture into a separatory funnel, using 25 cc. of benzene
to rinse the beaker. Shake well, separate and save both layers.
Extract the aqueous layer with 50 cc. of benzene, combine the
extract with the benzene-ether solution already collected and
give the solution a preliminary (superficial) drying by allowing
it to stand over 5 g. of anhydrous magnesium sulfate for 15
minutes.
Filter the solution into a distilling flask (250 cc.) and distil
the ether, water, and benzene, stopping the distillation when
the boiling point rises sharply and reaches a temperature of
1400. The residue in the flask is then nearly pure w-valeric acid.
Pour it into a distilling flask of suitable size (50 cc), connect this
to an air condenser, and distil the product into a weighed bottle.
The bulk of this should boil in the range 181-1850. Pure
72-valeric acid boils at 186° (corr.); the uncorrected boiling point
is about 50 lower. The yield ordinarily is 10-11 g. (see the re-
marks at the end of Procedure A). Test the solubility of the
substance in water and in sodium bicarbonate solution and
compare it in physical properties with acetic acid.
EXPERIMENT 14
ACETYL CHLORIDE
This particular acid chloride is always prepared by the action
of phosphorus trichloride on acetic acid, since acetyl chloride
(b.p. 510) is easily separated by distillation from the non-
volatile phosphorous acid formed (decomposing at about 200°).
Phosphorus pentachloride reacts equally well, but in this case
the second reaction product, phosphorus oxychloride (b.p. 1070),
distils at a temperature close enough to the boiling point of the
desired product so that the separation is not easily accomplished.
A similar objection may be raised to the use here of thionyl
chloride; an excess of the reagent must be employed, and since
it boils at 770 it cannot be removed effectively from the reaction
product.
The theoretical equation for the reaction involved is as follows:
3CH3COOII + PC13 —> 3 CH 3 COC1 + HsPOs
REACTIONS
1. Hydrolysis. — Cautiously add a few drops of acetyl chlo-
ride to a few cubic centimeters of ice-cold water and then shake
the test tube. Note that the acid chloride does not dissolve in
the water, but reacts with it to give soluble products.
2. Esters. — Place about i cc. of ethyl alcohol in a test tube
and add an equal volume of acetyl chloride by drops, while
keeping the solution cold by holding the tube under the tap.
Dilute the mixture with an equal volume of water, cool it again,
and if a layer of fragrant ethyl acetate fails to separate add a few
spatulafuls of sodium chloride to salt out the ester.
Repeat the test with one of the following alcohols, noting the
characteristic odor: iso-butyl alcohol, w-amyl alcohol, iso-amyl
alcohol, w-octyl alcohol.
EXPERIMENT 15
ALDEHYDES
1. Acetaldehyde
Of the two methods given below for the preparation of acetal-
dehyde, the first one represents a general procedure which may
be used for a variety of different aldehydes. It consists in the
oxidation of a primary alcohol with dichromate mixture. Since
an aldehyde is itself attacked by oxidizing agents even more
readily than the alcohol from which it is derived, it would be a
difficult matter to obtain a satisfactory conversion were it not
for the fact that the aldehydes are all much more volatile than
the corresponding alcohols. By dropping the alcohol onto the
oxidizing mixture and keeping this at a temperature below the
boiling point of the alcohol and above the boiling point of
the aldehyde, the aldehyde can be distilled from the reaction
mixture as soon as it is formed, and it is thus protected from
further oxidation. The preparation is a convenient one but the
yield is never high and the product usually contains the following
impurities: water, alcohol, acid, and the acetal, RCH(OR)2.
The second method, which consists in the depolymerization
of paraldehyde, is a special rather than a general method, for
only the first two members of the aldehyde series form readily
available polymers from which the monomeric aldehyde is easily
regenerated. The reaction, however, furnishes the most con-
venient means of obtaining pure acetaldehyde and it forms the
standard method of producing this compound whenever it is
required as a reagent in a laboratory preparation.
Acetaldehyde and its trimer, paraldehyde, form an equilibrium
mixture of the following composition:
Catalyst: II2SO4
3CH 3 CHO, b p. 21 0 ^ (CH 3 CHO) 3 , b.p. 1240
5% 95%
79
80 EXPERIMENT 15
2. Formaldehyde
Formaldehyde is a gas which liquefies only at —21°, and it
polymerizes easily in either the gaseous or liquid state. It is
obviously not a reagent which can be stored as such. The
commercial preparation known as " formalin," which is an
aqueous solution containing 35-40 per cent of formaldehyde and
some methyl alcohol, is a convenient source of this reagent for
use in reactions and preparations where the presence of water
and alcohol are not undesirable. Formalin is of course quite
unsuited for use in a Grignard reaction; here the most convenient
procedure is to generate gaseous formaldehyde by heating the
solid polymer trioxymethylene, (CH2O)3. The gas is bubbled
directly into the solution of the Grignard reagent. Where a
small water content is not objectionable, but where formalin is
found to contain an excessive amount of this diluent, it is often
convenient to employ methylal, CH2(OCH3)2 b.p. 420. In an
acidic medium, for example in a glacial acetic acid solution, this
substance hydrolyzes easily as follows:
CH2(OCH3)2 + H2O — > CH2O + 2HOCH3
fact that only the former, but not the latter compounds (one
exception) are easily oxidized and hence show a characteristic
reducing action. The permanganate test is not a good one, for
many alcohols and unsaturated hydrocarbons likewise reduce
this reagent. There are, however, two very mild oxidizing
agents which are reduced by aldehydes but not by these other
compounds. These reagents, (2) and (3) below, are solutions
containing complex cupric ions and complex silver ions, re-
spectively. Though these tests apply quite generally to alde-
hydes, and in almost all cases do not apply to ketones, there
is one type of ketorie which responds to the test like an alde-
hyde: the a-hydroxyketones easily reduce the reagents under
discussion.
A further distinction can be made, however, by taking ad-
vantage of another property characteristic of the aldehydes,
namely, the ease with which they are reduced. They show
oxidizing properties not shared by any of the ketones, and it is
on this fact that the sensitive Schiff test is based.
A ketone is often recognized simply from the observation
that it is found to be a carbonyl compound but does not respond
to any of the tests for aldehydes. Positive tests are available,
in fact, only for the methyl ketones (e.g., RCOCH3), and even
then the reactions must be applied with some discrimination.
These tests are listed below as numbers 5 and 6.
While the emphasis in this discussion has been placed on the
diagnostic value of the various reactions, the uses of some of
them in preparative work should not be overlooked in carrying
out the experiments.
1. Phenylhydrazine. — The test is varied slightly according
to the solubility of the compound to be studied.
(a) Water-soluble compounds: To about 3 cc. of water add 5
drops of the phenylhydrazinei and 5 drops of glacial acetic acid
(dropping tube) and make sure that a clear solution is obtained
(add more acetic acid if necessary). Now add 5 drops of the
1
Phenylhydrazine is poisonous; take particular care to avoid getting it on the
skin. If spilled, wash it off with dilute acetic acid and then with soap.
86 EXPERIMENT 16
iodine in potassium iodide,1 and then add 10 per cent alkali drop
by drop with shaking until the brown color of the iodine is dis-
charged and the solution is either colorless or faintly yellow.
Note the odor; see if there is a crystalline precipitate, which,
of course, will be very small. In case the iodoform is not pro-
duced at once, warm the test tube for a minute or two in a beaker
of water at 6o° (alcohols react more slowly than do carbonyl
compounds).
Test. — (a) either acetone or acetaldehyde; (b) either ethyl
alcohol, isopropyl alcohol, or s^c.-butyl alcohol; (c) aceto-
phenone, C 6 H 5 COCH 3 .
QUESTIONS
1. What conclusions can you draw from the results of your tests
concerning the reactivity of compounds containing the phenyl group
(C6H5—), as compared with the corresponding methyl or ethyl com-
pounds? Make as many comparisons as possible.
2. How does formaldehyde compare in reactivity with the other
aliphatic aldehydes?
3. What test would you select for distinguishing between an alde-
hyde and an a-hydroxy ketone?
4. Only one of the above tests could be used to distinguish between
the compounds: C6H6COCH3>and C6H5COCH2CH3 (acetophenone
and propiophenone). What is the test?
5. How would you proceed to prepare pure acetone, starting with
the pure, crystalline bisulfite addition product?
6. Outline the experimental procedure which you would use to
separate a mixture of pentanone-2 (b.p. 1020) and pentanone-3
(b.p. 101 0 ).
7. Suppose that it is desired to separate a mixture of an aldehyde
and a ketone which does not form a bisulfite addition product, and
suppose that they are both solids; how would you proceed? (Recall
the procedure used in Experiment 6.)
8. How would you test a sample known to be one of the following
compounds: hexanol-i, hexanol-2, or hexanone-2?
1
Prepared by dissolving 25 g. of iodine in a solution of 50 g. of potassium iodide
in 200 cc. of water; the iodine is largely present in the form of the molecular com-
pound, KI.I2.
EXPERIMENT 17
ACET AMIDE
The conversion of an acid into its amide is an operation which
is often carried out as a step in the preparation of an amine ac-
cording to the method of Hofmann or in transforming an acid
into its nitrile. Amides are also of use in the identification of
acids, for they are usually crystalline solids of characteristic
melting point even though the acids from which they are de-
rived are liquid substances.
Amides are most commonly prepared by the action of ammonia
on either the chloride or the ester of the acid in question. In the
majority of cases the acid chloride method is preferable because
this type of derivative reacts more rapidly with ammonia than
do the esters and because an acid chloride can be obtained very
rapidly in quantitative yield in a condition suitable for reaction
with ammonia. (Seepage 220.) If the amide is not appreciably
soluble in cold water, the ammonium chloride formed in the
reaction is easily eliminated by extraction with this solvent.
Acetamide, the simplest member of the series, is too soluble in
water to permit such a separation and in this case it is best to
extract the reaction mixture with alcohol, which dissolves the
organic product and leaves a residue of ammonium chloride.
Since acetamide is only slightly soluble in ether the reaction can
be carried out by saturating absolute ether with dry ammonia
gas at — 200 and slowly adding acetyl chloride. Reaction takes
place at once and the ether is then decanted and the solid residue
extracted with alcohol.1
When acetamide is prepared from ethyl acetate, as in the
procedure given below, the isolation of the product is best ac-
complished by distillation. The ammonolysis of the ester is
much slower than that of the acid chloride and when the reaction
1
Govaert, Chemical Abstracts, 28, 740 (1934).
91
92 EXPERIMENT 17
in which R is the " phenyl " group C6H5, derived from the
aromatic hydrocarbon benzene, C6H6. The aldehyde used is
benzaldehyde, C6H6CHO, and the product to be synthesized is
mandelic acid, C6H5CH(OH)COOH. This is a natural sub-
stance, obtainable from bitter almonds. The synthetic material,
however, is not quite identical with the natural material because
the latter is optically active.
Write the equations and study the reactions before com-
mencing, in order that you may work intelligently and so that
you will know when to take particular pains to avoid breathing
traces of hydrogen cyanide which may be formed.
Caution: Potassium cyanide is extremely poisonous and in
contact with an acid it liberates the poisonous gas, hydrogen
cyanide. The reagent may be used with perfect safety, but it
is necessary to adhere scrupulously to the following rules:
Manipulate the solid with great care to avoid spilling and do not
touch it with the fingers, particularly if you have an open cut
on your hand. Clean up at once any trace of material which
may be spilled. Wash the hands after manipulating the solid.
Pour any cyanide solutions which are to be discarded directly
into the drain pipe and wash down the sink with plenty of water.
Procedure. — To a solution of 16 g. of sodium bisulfite in 40 cc.
of water (250-cc. beaker) add 15 g. of benzaldehyde1 and stir the
mixture, well until the oily aldehyde is all converted into the
1
The benzaldehyde supplied should be free from appreciable quantities of ben-
zoic acid. See page 224.
94
SYNTHESIS OF MANDELIC ACID 95
The yield is not good, but this is offset by the cheapness of the
reagents.
Pinacol possesses the property, unusual for an alcohol or a
glycol, of forming a crystalline hydrate. Pinacol hydrate,
which contains no less than six molecules of water of crystal-
lization, is a convenient form in which to isolate the product of
the above reaction and to separate it from unreacted acetone
and from the isopropyl alcohol formed.
Procedure. — In a 500-cc. round-bottomed flask equipped
with an efficient reflux condenser place 8 g. of magnesium turn-
ings1 and 100 cc. of dry benzene.2 The apparatus should be
thoroughly dry, as in a Grignard reaction. A solution of 9 g.
of mercuric chloride in 75 cc. of dry acetone3 is placed in a small
dropping funnel which is fitted into the top of the condenser by
means of a grooved cork. Add about one-fourth of this solution,
and if the reaction does not start in a few minutes, as indicated
by a vigorous ebullition, warm the flask gently on the steam
bath, being ready to plunge the flask into cold water if it becomes
necessary to moderate the reaction. Once started, the reaction
will proceed vigorously at this stage without further heating.
Run in the remainder of the acetone solution at such a rate as to
keep the reaction in progress. The boiling should be vigorous,
but some cooling may be necessary in order to prevent the escape
of uncondensed acetone. After 5-10 minutes the reaction slows
down, and heat is then applied from the steam bath to keep the
mixture boiling briskly for one hour longer. The flask should
1
The very fine turnings preferred for a Grignard reaction are not essential;
a less expensive grade is adequate.
2
The benzene is dried by distilling until the distillate is no longer cloudy (10-15
per cent) and rejecting the distillate.
3
The acetone is refluxed with calcium chloride for 2 hours (or, better, allowed
to stand for 2 days with the drying agent) and distilled.
PINACOL HYDRATE 99
Pinacolone Rearrangement
When heated with either mineral or organic acids pinacol
undergoes a rearrangement with loss of a molecule of water to
give a ketone known as pinacolone:
CH3 CH, CH3
I I I
CH3-C C-CH8 y CII3-C C - C H 3 + H2O
II I II
OH OH CHS O
The acid also can be treated with a dehydrating agent, and in the
case of a dibasic acid of the type of succinic acid this direct
method is the only one which is applicable. The dehydration
can be accomplished conveniently with the use of either acetic
anhydride or acetyl chloride:
CH.COOH f (CH3CO)2O |' * x f 2CH3COOH
or
I + < or >- O+1
CHsCOOH ', CH3COC1 I / , CII3COOH + HC1
CH2CO
The dehydration is very rapid and when acetyl chloride is used the
course of the reaction can be followed from the evolution of gase-
ous hydrogen chloride. A distinct advantage of the method is
that the anhydride formed is not contaminated with any inorganic
reagents, and that the acetic acid which is produced serves as a
solvent for the crystallization of the anhydride. The proce-
dure may be used for preparing the anhydrides of glutaric, maleic,
and phthalic acid, and of many other compounds of the same
type.
Succinic anhydride is a useful compound, for it affords a means
of obtaining a variety of interesting compounds which cannot be
prepared directly from the acid. Thus on alcoholysis succinic
anhydride yields the monomethyl ester, I; the acid amide, II,
CH2CO
CH2COOCH3 CH 2 CONH 2
CH2:C
2COOH CH 2 COOH
:H
II III
103
104 EXPERIMENT 20
QUESTIONS
1. How could succinic acid be converted into /3-amino propionic
acid?
2. Devise a method for the resolution of a ^-alcohol, assuming that
an optically active derivative of aniline is available, and noting that
the succinanilic acid, like other acids, can be esterified without
culty.
EXPERIMENT 21
CHARACTERIZATION OF THE AMINES
QUESTIONS
1. How could you most easily distinguish between samples of
)3-naphthylamine and of acctanilide?
2. Would you expect the reaction product from benzenesulfonyl
chloride and ammonia to be soluble or insoluble in alkali?
3. Is it safe to conclude that a substance is a tertiary amine because
it forms a picrate?
4. Why is it usually true that amines which are insoluble in water
are odorless?
5. Technical dimethyl aniline contains traces of aniline and of
methyl aniline. Work out a method of freeing it completely from
these impurities. (Note that acyl derivatives of amines are not basic
substances.)
6. How would you prepare aniline from aniline hydrochloride?
EXPERIMENT 22
PHYSIOLOGICAL FORMATION OF HIPPURIC ACID
Hippuric acid appears to be formed in the kidney of an animal
by the union of benzoic acid and glycine:
Enzyme
C 6 H 5 COOH + H2NCH2COOH > C 6 H 6 CONHCH 2 COOH + H 2 O
Benzoic acid is not attacked by most chemical oxidizing agents
and it likewise resists oxidation in the organism. By reaction,
or " conjugation," with glycine from the blood stream it is
rendered harmless and eventually excreted in the urine in the
form of hippuric acid. The mechanism for the elimination of
benzoic acid is of importance on account of the fact that certain
foodstuffs, particularly vegetables and fruits, contain substances
which are converted into this acid by degradation in the body.
Benzoic acid apparently can be formed also during periods of
fasting by the metabolism of those amino acids which contain
aromatic rings.
Hippuric acid occurs abundantly in the urine of the horse, and
of other herbivorous animals, and indeed this at one time repre-
sented the chief source of commercial benzoic acid, which is easily
produced by hydrolysis of the peptide-like acid. Human urine
normally contains much smaller quantities of the acid, the aver-
age output amounting to about 1 g. per day. The production is
considerably increased by special diets; thus one experimenter
reports the isolation of 10 g. of hippuric acid after eating 450
g. of prunes, and of 4.7 g. from 305 g. of cranberries. It is
believed that quinic acid (C6HnO4COOH) is the chief precursor
of benzoic acid present in these fruits.
Interesting results have been obtained in special feeding
experiments with benzoic acid itself, the acid being ingested in
the form of a solution of the sodium salt. It requires only about
114 EXPERIMENT 22
more than an hour or two before use, add 5-10 cc. of toluene to
prevent decomposition, and then separate this when ready to
proceed further.
For every 100 cc. of urine add 4 cc. of concentrated hydro-
chloric acid and note if a precipitate forms. (If some acid
separates at this point, collect it and combine it with any further
material obtained by the following procedure.) Now add am-
monium sulfate (25 g. per 100 cc. of urine) in portions, stirring
well so that it will all dissolve. The hippuric acid may separate
even before all of the added solid has dissolved, or it may deposit
only after the solution has been well cooled and allowed to stand
for several hours. Collect the precipitated material by suction
nitration, wash it with a small quantity of cold water, and crystal-
lize it from water, using a little animal charcoal to decolorize
the solution. Since hippuric acid is fairly soluble in cold water,
avoid an excess of solvent and cool the solution at o° before
collecting the crystals. Record the melting point and the yield
of the purified product (m.p., pure, 187.50). The average yield
is 3 g-
Identification. — A sample of hippuric acid for comparison
is to be prepared synthetically from benzoyl chloride (C6H5COC1)
and glycine. These reagents combine easily in the presence of
alkali, and the reaction is an example of the general type known
as the Schotten-Baumann reaction. (Compare the Hinsberg
test, Experiment 21.)
In a test tube, or better in a small, stoppered bottle, dissolve
1 g. of glycine in 5 cc. of water, add 1.5 cc. of benzoyl chloride,
and then sufficient 10 per cent sodium hydroxide solution to
render the mixture alkaline. Shake vigorously, releasing the
pressure occasionally and keeping the mixture distinctly alkaline,
until there is no longer any odor of benzoyl chloride (open the
stopper carefully, smell with caution). When the reaction is
complete, pour the alkaline solution into a flask, cool it in an
ice bath, and acidify with concentrated hydrochloric acid. The
precipitated hippuric acid, which contains a certain amount of
benzoic acid, is collected by suction filtration and washed with
Il6 EXPERIMENT 22
water. The greater part of the benzoic acid is then washed out
with ether; the solvent being poured in portions onto the
crystalline cake and allowed to drain before applying the suction.
Crystallize the product from water and compare it by melting
point determinations with that obtained above.
EXPERIMENT 23
UREA FROM URINE
some time preceding the actual working period, for the operation
requires no attention but takes some time.1 To make the evapo-
ration efficient use the largest ring of the steam bath that will
support the dish and insert a match stick between the dish and
the ring so that the steam will rise around the sides of the dish.
The process then can be completed in about 4 hours and without
using an excessive amount of steam. The evaporation is to be
continued until a thick syrup is obtained.
To this syrup 100 cc. of alcohol is added and the mixture is
stirred well and warmed gently on the steam bath so that a good
extraction is obtained. After 5-10 minutes the clear solution is
decanted and the residue is treated in the same way with a
second 100-cc. portion. The combined alcoholic solutions are
boiled gently for a few minutes with 1 g. of animal charcoal and
filtered through a large paper into a 400-cc. beaker. The alco-
hol is then evaporated until a thick, brown syrup remains.
This can be accomplished very quickly if the beaker is so ar-
ranged that it extends through one of the rings into the steam
bath, and if a towel is wrapped around the beaker so that this
will be surrounded by steam and not just heated from the bottom.
Use a piece of porous pot and be careful of flames. After re-
moving the alcohol, the residual syrup is cooled thoroughly in a
salt-ice bath and 25 cc. of pure, concentrated nitric acid is
added by drops from a separatory funnel, the mixture being
stirred continually and kept cold. The oil gradually changes to
a paste of the solid urea nitrate. This is allowed to stand in
ice for fifteen minutes and then the paste is filtered by suction,
using a hardened filter paper or a sintered-glass funnel. The
filter cake is washed well with ice-cold nitric acid (1 : 1) to re-
move the yellow mother liquor, and sucked as dry as possible.
The filter flask is then cleaned and replaced and the urea nitrate
is washed with an ice-cold mixture of 15 cc. of ether and 5 cc.
of alcohol. This removes any free nitric acid and hastens the
1
In case the hood facilities are limited the evaporation can be carried out in a
2-1. flask evacuated at the water pump and kept warm in a water bath, the level
of which is a little higher than that of the liquid in the flask.
UREA FROM URINE 119
(Galactose) (Glucose)
r
O
CH-
CHOH
CHOH
I
CHOH
I
0
CHOH
I
I
CHOH
CHOH
I
H
-CH
I
CHOH
I
CHOH
I
CHOII
O
CHO
I
CHOH
I
CHOH
I I I
-CH CH CH CHOH
I I I I
CH 2 OH CH2OH CH2OH CH 2 OH
Cyclic form Aldehyde form
Lactose
(i-Galactosido [i,5]-4-glucose)1
-Cll- CHOH CH 2 OH
I I
CHOH CHOII CHOII -c
I I I I
O CHOH O CHOH O CHOH CHOH
I I I I O
CHOH -CH CHOII CHOH
I I I
CH CH -CH CH
I I I I <
CH 2 OH CH 2 OH CII 2 OII CH 2 OH
Maltose Sucrose
(i-GIucosido [i,5]-4-glucose) (i-Glucosido [i,5]-2-fructoside [2,5])
titration is reached when the deep blue color of the solution just
disappears. This should require 10 cc. of the glucose solution.
The reaction is not instantaneous and more time must be al-
lowed between successive additions of solution than in an acid-
base titration.
Osazones. — The presence or absence of a free carbonyl
group in a sugar is most easily demonstrated by testing with
Fehling's solution. If a positive test indicates that the substance
in question is a reducing sugar, then it can be foretold that the
compound will react with phenylhydrazine to form an osazone,
and this latter reaction is often of considerable service in furnish-
ing further information concerning the substance under investi-
gation. The reaction is easily carried out and the formation
of the osazone becomes apparent by the separation from an
aqueous solution of a crystalline, yellow, usually sparingly
soluble precipitate. A determination of the melting point or
an examination under the microscope of the crystalline form may
serve to identify the osazone and hence the sugar from which it
was produced. It must be remembered, however, that phenyl-
hydrazine attacks the first two carbon atoms of the sugar and
that those sugars which have the same configurations below the
second carbon atom yield identical osazones. This is true, for
example, of glucose, fructose and mannose, all of which give
rise to one and the same osazone. The melting points of the
osazones are fairly well defined and characteristic, but they vary
considerably with the rate of heating, and it is necessary to
adopt a carefully standardized procedure in order to obtain
significant results. (The heating bath should rise i° every two
seconds.)
It is often possible to make certain inferences from the osa-
zone reaction without collecting and examining the product.
The different sugars vary considerably in the rate with which
they react with phenylhydrazine, and it is thus well to follow a
standardized procedure and to note the time required for the
separation of the crystals. The experiment below will reveal a
characteristic difference in the rate of reaction of two isomers,
SUGARS 125
QUESTIONS
1. What test do you regard as the most satisfactory one for dis-
tinguishing between glucose and fructose?
2. Outline the steps which you would take to show that maltose
is a reducing sugar, that it is a disaccharide, and that it is composed
solely of glucose units.
3. On hydrolyzing a solution of sucrose and then adding phenyl-
hydrazine, there is obtained a single osazone. Would this also be
true for lactose?
4. Work out a method for the quantitative determination of sucrose
through the use of Fehling's solution.
5. Do your own experiments furnish any indication that glucose
does not exist in solution entirely in the aldehyde form?
EXPERIMENT 25
POLYSACCHARIDES
A. Starch
Starch is a complex carbohydrate of high molecular weight
having the composition (CgHioOs),. It is known to be composed
of glucose units, for this is the sole monosaccharide obtained on
complete hydrolysis of the material by means of hydrochloric
acid. Under the influence of certain enzymes hydrolysis pro-
ceeds just as easily as with a mineral acid but not as far. The
enzyme diastase, which is present in malt, brings about hy-
drolysis to maltose. The saliva contains an enzyme, ptyalin,
which likewise converts starch largely into maltose. This
disaccharide is susceptible to hydrolysis by hydrochloric acid
and hence cannot be isolated in the reaction of starch with this
acid although it undoubtedly is an intermediate product. It is
probable that starch is made up of a series of maltose units
linked together by oxygen bridges by a process akin to a polymeri-
zation. Starch occurs in plants in the form of granules and it
is not directly soluble in water. When it is boiled with water the
granules swell and the material gradually passes into solution,
possibly as the result of a partial depolymerization.
Even soluble starch must consist of fairly large molecules, for
the solution is colloidal. This can be shown clearly by a simple
dialysis experiment. If a solution containing both starch and
glucose is placed in a parchment bag and this is left suspended
in pure water for some hours, tests will show that glucose has
diffused through the parchment and that the starch has not.
Starch is easily recognized, and at the same time distinguished
from the other carbohydrates, by the characteristic blue color
of some product of unknown nature which is formed by reaction
129
130 EXPERIMENT 25
B. Cellulose
Cellulose, like starch, has a composition corresponding to the
formula (C6Hio05)^, and, like it, is composed entirely of glucose
units. It differs distinctly from starch in being insoluble in water
and much more resistant to hydrolysis, and from this it is inferred
that the molecular size is considerably greater. The digestive en-
zymes are incapable of bringing about the hydrolysis of ordinary
forms of cellulose; hydrolysis by mineral acids is a slow process,
but yields of glucose as high as 95 per cent of the theoretical
amount have been reported. By carrying out the hydrolysis in
the presence of acetic anhydride, the acetate of an intermediate
disaccharide has been isolated. This is known as cellobiose and
it has the structure of i-glucosido [i,5]-4-glucose. By reference to
page 123 it will be seen that this is also the structure of maltose,
the disaccharide obtained from starch. The disaccharides mal-
tose and cellobiose are not identical and the difference between
them appears to be of a stereochemical nature: one is derived
from a-glucose and the other from /3-glucose.
Unlike starch, cellulose is but little affected by being boiled
with dilute hydrochloric acid. This stability is probably due
both to the insolubility of the material in water and to a low
degree of chemical reactivity. Even a strong solution of sulfuric
acid prepared from two volumes of concentrated sulfuric acid
and one volume of water produces only a superficial change.
Filter paper left in such a solution (cold) for just 15 seconds and
then washed with water and ammonia is changed somewhat in
appearance and in strength without being appreciably hydro-
lyzed. This is parchment paper. To bring about complete
hydrolysis, cellulose is dissolved in concentrated sulfuric acid
and the sticky mass is boiled for some time with water.
132 EXPERIMENT 25
I I
,011 HO-C- .O-C-
Cu (N + I >- Cu (X I + 2H2O
OH H O - C - O-C-
134 EXPERIMENT 25
+ H2SO4
This is much more convenient than the older process in which the
solution containing sulfuric acid and the sulfonic acid is first
neutralized with barium carbonate. The soluble barium sul-
fonate is then extracted from the precipitate of barium sulfate
and treated with an exactly equivalent amount of dilute sulfuric
acid. Barium sulfate again precipitates and the filtered solu-
tion of the free sulfonic acid is then treated with just enough
sodium hydroxide to form the sodium salt, and the solution is
evaporated to obtain the solid.
Where a substitution reaction is likely to give a mixture of
products it is of prime importance to be able to determine the
purity of the product obtained and to establish its identity.
Since the metal salts of the sulfonic acids do not melt but only
decompose on being heated to a high temperature, it is necessary
to convert them into derivatives characterized by good melting
points. The most convenient type of derivative is described at
the end of the procedure.
Procedure. — In a 200-cc. round-bottomed flask provided with
a reflux condenser place 32 cc. (0.3 mole) of purified toluene1 and
19.0 cc. of c.p. concentrated sulfuric acid, add a clay boiling
chip and heat the mixture on an asbestos gauze while shaking
constantly with a rotary motion. The acid should not be thrown
onto the cork. When the upper layer of toluene begins to boil
cut down the flame to about one inch and note the time. Con-
tinue to heat gently and to swirl the mixture very thoroughly
every two or three minutes so that the two layers are well mixed
and able to react. With proper heating there is little activity
in the toluene layer and just a slow dropping from the con-
denser. When shaken there will be a mild rush of condensate.
Too strong heating only drives the toluene out of the reaction
1
Ordinary toluene contains thiophene derivatives which cause a blackening of
the reaction mixture. The hydrocarbon supplied for the experiment should be
purified by the sulfuric acid treatment described on page 364.
SODIUM ^-TOLUENE SULFONATE 139
QUESTIONS
1. Explain why, when the solution saturated at the boiling point
with both sodium chloride and sodium />-toluene sulfonate cools, it is
the latter rather than the former salt which crystallizes.
2. Supposing that you were working with a rare hydrocarbon in
place of toluene, how would you recover the unsulfonated material?
3. Potassium ^-toluene sulfonate is less soluble in water than the
sodium salt; how would you proceed to prepare it from your sample
of sodium salt?
EXPERIMENT 27 *
SODIUM ^-NAPHTHALENE SULFONATE2
H 2 SO 4 >• + H2O
TEST REACTIONS
In addition to the tests already given in Experiment 21 for
the recognition of primary amines, there are certain others which
are sometimes useful and which apply in particular to the pri-
mary aromatic amines. The following tests may be carried out
conveniently during the steam distillation. A few drops may be
used from the first part of the distillate, or an equivalent amount
of water saturated with aniline will suffice.
1. Bromination. — To 2-3 cc. of a dilute aqueous solution of
aniline add bromine water drop by drop until the solution be-
comes faintly yellow. The precipitate is tribromoaniline, m.p.
116°, a derivative useful for the identification of the amine.
The test is of special value because of the very small amount of
material required and because it can be applied to an aqueous
solution and does not require the isolation of the dry amine.
Most aromatic amines react in a similar fashion: all free posi-
tions ortho or para to the amino group are substituted by
bromine atoms. Thus o-toluidine and ^-toluidine form dibromo
derivatives melting at 500 and 73 °, respectively; w-toluidine
forms a tribromo compound melting at 97°.
2. Runge's Reaction. — To a solution of one drop of aniline
in about 40 cc. of water add a filtered solution prepared by
shaking a few lumps of bleaching powder with 2-3 cc. of water.
A violet color is produced.
This sensitive test is peculiar to aniline, and may be used for
detecting small quantities of benzene or of nitrobenzene after
these have been converted into aniline. The bleaching powder
oxidizes this base to a complex dye of structure not yet known.
3. Isonitrile Reaction. — To 2 drops of aniline add 2 cc. of
alcohol, 10 drops of concentrated potassium hydroxide solution,
152 EXPERIMENT 29
Alternate Procedure
(For use when zinc is not available)
To a i-l. round-bottomed flask (which is to be used later in
the steam distillation) add 30 g. of iron powder (reduced by
hydrogen) and 40 cc. of water. Warm the liquid to 850, add
i£ cc. of concentrated hydrochloric acid, attach a reflux air
condenser to the flask and through it add a small portion
(about 4 cc.) of the total amount of nitrobenzene to be reduced,
24.6 g. (20.5 cc). Heat the mixture on the steam bath for
2-3 minutes and then, while holding the flask with the condenser
in a slanting position, shake quite vigorously; a mirror of oxide
quickly appears on the walls of the flask, the mixture becomes
very hot, and vapors rise in the condenser. Add the rest of the
nitrobenzene in 3- to 4-cc. portions over a period of about 10
minutes, shaking the mixture as above after each addition;
occasional cooling of the flask with tap water may be necessary
to prevent loss by distillation. After all of the nitro compound
has been added, shake the flask until an evident cooling of the
mixture indicates that the exothermic reaction has ended (about
5 minutes).
Cool the reaction mixture, arrange the flask for steam dis-
tillation, and conduct the distillation and subsequent operations
according to the directions beginning with line 6 on page 150.
The yield of colorless aniline is 15 g.
STEAM DISTILLATION
This important operation consists in volatilizing an organic
compound which is insoluble or sparingly soluble in water by
passing steam into a mixture of the substance with a little
water. The organic compound, if it has suitable properties,
will distil with the steam and, being immiscible with the water
in the condensate, it is easily separated whether it is a solid or a
liquid substance. Of the compounds which do not dissolve
readily in water only a limited number have the added property
of being volatile with steam; hence this type of distillation is
a highly selective process and wherever it is applicable it usually
is found to have certain distinct advantages. It often affords
an excellent means of separating an organic reaction product
from an aqueous mixture containing inorganic salts, or of sepa-
rating one compound from a mixture with other organic com-
pounds which do not share the required property. Thus tri-
phenylcarbinol (Experiment 12) is best freed from diphenyl, an
unavoidable by-product, by distillation of the latter substance
with steam. The isomers o-nitrophenol and ^-nitrophenol are
commonly obtained together and separated by steam distil-
lation, since only the former isomer volatilizes under these
conditions. A simple way to determine if a substance known to
be but sparingly soluble in water is volatile with steam is to boil
a mixture of a test sample and water under a cold finger
(page 64). A turbidity or cloudiness in the condensate will
show that the substance has volatilized.
Another distinct advantage of the process is that the tempera-
ture at which a steam distillation occurs is always lower than the
boiling point of water under the same conditions, and hence in
many cases far below the boiling point of the organic substance
which is volatilized in this way. This remarkable fact, which is
explained below, makes possible the purification by low-tempera-
153
154 STEAM DISTILLATION
60
200 400 600 800
Vapor Pressure (mm. of Mercury)
FIG. 13. — Vapor Pressure Curves
Water
-Adapter, A
Adapter
HYDROLYSIS
^-Bromoaniline, m.p. 66°, can be obtained by the hydrolysis
of the acetyl derivative with either acid or alkali. The reaction
is to be carried out here as a test, rather than as a preparation,
and there is a slight difference in the conditions most satisfactory
in each case. For the preparation of the amine in quantity it is
expedient to use considerable alcohol as a solvent; but the
presence of much of this solvent is objectionable in a test, for it
may obscure the true solubilities of the compounds concerned
in water and in acids.
Alkaline Hydrolysis. — Using the cold finger shown on
page 64, boil rather vigorously a mixture of 0.2 g. of ^>-bromo-
acetanilide, 5 cc. of 20 per cent sodium hydroxide solution and
1 cc. of alcohol for 15-20 minutes. Note any change in the
appearance of the product and see if it is consistent with the
melting points of the compounds concerned. Cool the mixture
with shaking; extract a small quantity of the product on the
end of a stirring rod and see if the material, or at least a part
of it, will dissolve in dilute hydrochloric acid and precipitate
again on neutralizing the solution. Such behavior is character-
istic of an amine.
Acid Hydrolysis. — In the same apparatus boil a mixture of
0.2 g. of />-bromoacetanilide, 5 cc. of 20 per cent hydrochloric
acid (equal parts of the concentrated acid and water) and 1 cc.
of alcohol for 15-20 minutes, or until the reaction is complete.
It is well to shake the tube occasionally in order to dislodge
the solid from the walls. When a clear solution is obtained,
cool this under the tap and note the character of the crystalline
^-BROMOACETANILIDE 169
HYDROLYSIS
^-Nitroaniline, m.p. 146°, can be prepared in satisfactory
manner by the acid hydrolysis of the acetyl derivative, but
alkaline hydrolysis in this particular case is not advisable for the
reason that the />-nitroaniline may be partially converted into
^-nitrophenol by this reagent. The amino group is rendered
somewhat mobile by the unsaturated group in the para position,
and it is susceptible to alkaline hydrolysis. In the presence of
an acid, on the other hand, the amino group is protected by
salt formation.
Hydrolyze a test portion of the product by the second method
given on page 168.
EXPERIMENT 33*
/3-NAPHTHOL
CioH,S0 3 Na + KOH —> C10H7OK + NaHSO 3
C10H7OK + HCI C10H7OH + KC1
minute or two with 0.5 g. of animal charcoal, and filter the solu-
tion into an Erlenmeyer flask. Remove the bulk of the benzene
by distillation from the steam bath, using a bent tube to make
connection to the condenser. Let the flask rest below the rings
and wrap it with a towel. Distil the oil which remains from a
small distilling flask over a free flame using an air condenser.
The fore-run will contain some benzene and must be kept away
from the flame. Pure diphenylmethane boils at 2620, crystal-
lizes to a colorless solid melting at 26 -27°, and has a pleasant
orange odor. Collect the fraction boiling at 250-275° and see
if it can be caused to solidify by cooling in ice and scratching,
or by seeding with a crystal of the pure material. If this is not
the case redistil the product, collecting the fraction boiling at
255-2650. Allow the solid to melt while stirring it with a ther-
mometer. The temperature rises steadily at first and then
remains essentially constant for a time until most of the solid
has melted; this is the melting point. Material prepared as
above usually melts in the range 20 -230; yield 15-20 g.
Note that there is a considerable quantity of high-boiling
residue. This is known to contain anthracene (m.p. 217°),
o-dibenzylbenzene (m.p. 78°), and />-dibenzylbenzene (m.p. 86°);
these hydrocarbons all boil in the range 350-380°.
EXPERIMENT 35'
tert.-BUTYLBENZENE AND p-tert.-BVTYLPBENOL
(CH,).CC1.
(AlCls)
,. Suction
Pump
FIG. 20.• - Apparatus for Carrying Out the Friedel and Crafts
Reaction at a Low Temperature
butyl chloride layer, dry the liquid over calcium chloride, and
purify it by distillation. Yield, 45-50 g.; b.p. 50-510.
The Friedel and Crafts reaction is best carried out in a i-l.
long-necked, round-bottomed flask which can be used later for
steam distillation and which is fitted with a mechanical stirrer
and a dropping funnel fitted into a three-way addition tube as
shown in Fig. 20. By applying a very gentle suction the hydro-
gen chloride can be drawn into the trap and it is not necessary
to use a gas seal for the stirrer. For 50 g. of lerl.-hutyl chloride
use 50 g. of aluminum chloride and 175 cc. of dry benzene.
Place the halide in the dropping funnel and introduce the other
reagents to the reaction flask. Clamp the flask in a salt-ice
bath, set the stirrer in motion, and at once run in 2-$ cc. of the
halide from the dropping funnel in order to prevent the benzene
from freezing. Cool the mixture thoroughly before proceeding
further. It is well to stir the ice bath occasionally by hand.
Add the terL-butyl chloride in portions over a period of 6 hours,
stirring continuously and keeping the mixture at a temperature
of 0-5 0 .
Continue the stirring for one hour longer and then remove
the stirrer and add in small portions 150-200 g. of ice (hood),
shaking the mixture in an ice bath during the process. Add
50-100 cc. of cold water to complete the decomposition of the
intermediate product and then steam distil the mixture. After
separating the upper layer of benzene and ferf.-butylbenzene,
extract the water layer with two small quantities of ether and
combine the extract with the benzene solution. Dry thoroughly
over calcium chloride and fractionally distil the mixture twice,
using a column. In the second distillation retain the fraction
boiling at 164-1680. The pure material boils at 1670. Yield,
35-45 g-
Sodium ^-ferf.-Butylbenzene Sulfonate. — To 40 g. of tert.-
butylbenzene in a 250-cc. round-bottomed flask add slowly in
the course of 20 minutes 45 cc. of fuming sulfuric acid containing
15 per cent of sulfur trioxide. Keep the mixture at a tempera-
ture of 250 (thermometer in the liquid), shaking frequently.
182 EXPERIMENT 35
X
C6H4 X( ) O + C6H6 _ > . C6H4 ( C6H5 + HC1
CO / \COOH
^C=0:"' +H 2 0 — >
R/ ''• AICI2
(Actually the addition compound has twice the molecular weight
indicated, and aluminum chloride in most solutions has the
formula AUCle.1)
The example given in the present experiment, selected because
1
Kohler, American Chemical Journal, 24, 385 (1900); 27, 241 (1902).
183
184 EXPERIMENT 36
O + 2AIC13
o
QUESTIONS
1. What molecular proportion of aluminum chloride would you
use and what solvent would you employ for the Friedel and Crafts
condensation of (a) acetic anhydride with toluene; (b) succinic an-
hydride with naphthalene?
2. Would you expect that anisole, C6H5OCH3, would be capable
of forming a complex compound with aluminum chloride?
3. Why, in the purification of the crude o-benzoylbenzoic acid, is
the product dissolved in sodium carbonate solution rather than in
alkali?
4. What is the objection to the use of alcohol as solvent in the
Friedel and Crafts reaction? Ether?
ALTERNATE PREPARATIONS
o-(/>-Toluyl)-benzoic Acid. —
o-(3-Acenaphthoyl)-benzoic Acid. —
XOOH
Acenaphthene is a solid melting at 950 and in order to con-
dense it with phthalic anhydride a solvent inert to aluminum
chloride must be used. Dissolve 15 g. of acenaphthene and 15 g.
of phthalic anhydride in 75 cc. of purified tetrachloroethane
(see page 366) by heating in a 500-cc. long-necked, round-
bottomed flask designed for efficient steam distillation. No
condenser is required during the reaction but the flask should
be provided with a tube to conduct hydrogen chloride to a gas
trap. Cool the solution until the temperature registers 5° (some
solid may separate) and, keeping the flask in the ice bath, add
30 g. of aluminum chloride and connect the trap. Shake
thoroughly with good cooling for 10 minutes, remove the flask
from the cooling bath and allow the reaction to proceed at room
temperature for one-half hour with frequent shaking, when the
addition compound should have separated as a stiff paste. To
complete the reaction place the flask in a beaker of water heated
to 500 and allow it to stand for one-half hour. Work up the
product according to the procedure given above, making such
slight changes as appear advisable. Record your own procedure
and observations carefully.
Pureo-(3-acenaphthoyl)-benzoicacid forms colorless, anhydrous
crystals melting at 2000. If mechanical losses are minimized
by careful and thorough work (wash and rinse all flasks, funnels!),
it is possible to achieve a 96 per cent yield of material melting
within one or two degrees of the correct temperature. This
keto-acid is reported to undergo ring closure to an anthraquinone
only with great difficulty.
EXPERIMENT 37
ANTHRAQUINONE
O
CO
H 2 SO,
"COOH
flame until the yellow solution turns darker and somewhat red
and crystals of anthraquinone begin to separate (this occurs at
about 160°). Allow the tube to cool to room temperature,
dilute with water, force a wad of crystals into the end of the
tube with a stirring rod, decant the acid solution and wash by
decantation. Perform a vat test By this simple procedure
it is an easy matter to determine if a given acid is of the type
represented by o-benzoylbenzoic acid.
EXPERIMENT 38»
1-BENZOYLNAPHTHALENE
CO—(
Cu catalyst
3
4. C0 2
26O-27O
dioxide takes place more readily with the aromatic acids than
with the ordinary aliphatic acids, probably because the carboxyl
group is attached to another unsaturated group, that is, the
benzene nucleus. Oxalic acid, (COOH)2, has the somewhat
similar structural feature that two unsaturated carboxyl groups
are directly connected, and it likewise loses carbon dioxide
readily. The ortho-keto acid used here is decarboxylated with
particular ease, the reaction commencing at about 150°. It
should be noted that the catalyst is all-important, for without
it o-benzoylbenzoic acid is converted on heating (at 300-3 500)
chiefly into anthraquinone, water being eliminated rather than
carbon dioxide. One per cent of copper is enough to change
the entire course of the reaction, but the exact way in which it
functions is not yet clear. The metal itself is not the active cata-
lyst, for it is effective only after it has dissolved in the molten acid
to form a copper salt. In fact, since it dissolves rather slowly, it
is better to introduce the copper in the form of the normal copper
salt of o-benzoylbenzoic acid (CcHoCOCeKUCOO^Cu, for this
dissolves at once. It might be supposed that this is the true
catalyst, but observation of the color changes in the course of
the reaction will show that this cannot be the case. The matter
still awaits solution.
The unpurified, hydrated o-benzoylbenzoic acid prepared as
in Experiment 36 is suitable for use as the starting material.
It is well to drive off the water of crystallization before adding
the catalyst for otherwise this water will cause trouble at the
high temperature and interfere with the even heating. The
decarboxylation must be carried to completion, for any un-
changed o-benzoylbenzoic acid will be converted into anthra-
quinone when the temperature is raised for the distillation.
Overheating will also lead to contamination with yellow anthra-
quinone.
It is of interest that benzophenone exists in two different
forms. The ordinary, or stable form crystallizes easily and
forms opaque prisms melting at 48°; the labile form solidifies
only very slowly and gives transparent crystals melting at 26C.
BENZOPHENOXE 199
The two forms have identical chemical properties and they are
interconvertible. If the stable form is introduced carefully into a
distilling flask in such a way that no tiny particles (" seed ")
lodge in the side tube or above it, and if the material is slowly
distilled from clean, seed-free apparatus, the distillate is a water-
clear liquid which can be cooled to 0° without solidifying. This
is the labile form in liquid condition. If the liquid is rubbed
against the containing walls, or if it is inoculated with a trace
of the stable form of benzophenone, it suddenly changes to the
stable form and solidifies. There is a considerable temperature
rise, due to a combination of the heats of isomerization and of
crystallization. If the liquid labile form is allowed to stand in
an ice chest for several hours or days it sometimes solidifies, and
it then remelts at 260. The solid material, however, is not easy
to obtain since it appears inadmissible to try to induce crystal-
lization either by rubbing or by the use of solvents, for this only
leads to a change to the more stable form.
Procedure. — Place 24.4 g. (o. 1 mole) of o-benzoylbenzoic
acid monohydrate in a 50-cc. distilling flask supported by means
of a clamp fitted with a strip of asbestos paper (no rubber!).
Heat the flask gently with a free flame (no gauze) with shaking
until the solid is all melted and some of the water is expelled.
Then insert a cork stopper carrying a thermometer so arranged
that the bulb is completely submerged in the molten acid. Con-
nect the side tube of the flask to the suction pump and again
heat gently for a few minutes in order to eliminate the water.
Bring the temperature of the liquid to 200° and play the flame
gently over the upper parts of the flask in order to expel any water
which may condense here. Then disconnect the tube leading
to the suction pump, remove the stopper and add 2 g. (0.004
mole) of the copper salt of o-benzoylbenzoic acid (end desk1),
1
Enough copper salt for 12 runs is prepared as follows: Dissolve 24.4 g. of
o-benzoylbenzoic acid monohydrate and 5.3 g. of anhydrous sodium carbonate in
300 cc. of water by boiling, cool to 50° by the addition of ice and add a solution of
12.5 g. of copper sulfate crystals in 25 cc. of water. The voluminous blue-green
precipitate is a hydrate; heat and stir the suspension until this changes to the
granular, anhydrous salt. Collect and wash this material and dry it at no 0 ;
2OO EXPERIMENT 89
using a dry funnel or a paper cone so that the salt cannot lodge
in or above the side tube. Replace the thermometer and con-
nect the outlet of the flask by means of a section of rubber
tubing to a glass tube resting in a graduate in which there is just
enough water to seal the tube, so that the evolution of carbon
dioxide can be followed. More water may be dangerous in
case of a suck-back. Heat the flask with a small free flame and
bring the temperature of the liquid to 2650 without delay, and
by constant adjustment maintain a temperature as close to this
as possible throughout the reaction. There should be a steady,
vigorous evolution of gas and in 20-25 minutes metallic copper
should separate from the clear solution. In another 5 minutes,
with the temperature still at 265°, the bubbling in the trap
should cease. When this point is reached the trap is discon-
nected, the flame is removed, and the thermometer is raised
to the usual position for distillation. Using an air condenser,
distil the benzophenone into a weighed 50-cc. Erlenmeyer flask,
using a free flame and no gauze. The true boiling point of benzo-
phenone is 3060, but with so much of the thermometer thread
extending out of the heated area the uncorrected boiling point
may be as low as 204°. The condensate is usually colorless or
light yellow. Continue the distillation until there is a marked
rise in the boiling point (4-5°) or until the distillate becomes
dark yellow.1
Record the weight of the crude benzophenone (15-18 g.) and
see if it will solidify on cooling under the tap or on being rubbed
with a stirring rod. Unless the laboratory air carries sufficient
ordinary benzophenone to act as seed, one usually obtains at
this point the labile form, which (particularly since it is not
quite pure) is very reluctant to solidify. If this is the case fix a
barely visible particle of ordinary benzophenone on the end of
a stirring rod and rub it into the liquid against the side of the
yield, 24-25 g. (The salt separates as an oil if the solution is at the boiling point
when the copper sulfate is added.)
1
The dark residue in the flask can be loosened and the mass of copper dislodged
by adding benzene and heating the flask on the steam bath for one-half hour.
The dark solution is decanted and if necessary the process is repeated.
BENZOPHENONE 2OI
C I I 3 \ ^ / O H Sunlight,
4.™.>C,0
C—C — y C + O= C
CeHs 7 I I XC6H6 CeHij/ X O H X
C6H5
OH OH
Benzopinacol, m.p. 1890 Benzhydrol, m.p. 68° Benzophenone, m.p. 480
under a reflux condenser until the crystals are all dissolved, and
then reflux the red solution for 5 minutes. On cooling the pi-
nacolone separates to form a stiff paste. Thin this with alcohol,
collect the product and wash it free from iodine with alcohol.
The material should be directly pure; yield, 95 per cent.
EXPERIMENT 41
AZO DYES
The coupling of benzene diazonium chloride with phenol, or
with one of the cresols or naphthols, gives rise to a type of azo
compound which is highly colored, but which contains no acidic
or basic groups, which is not soluble in water, and which thus
lacks two of the properties ordinarily required of a direct dye-
stuff. The introduction of a sulfonic acid group is sufficient to
confer on the substance the desired properties, but the direct
sulfonation of an azo compound often presents some difficulties.
A much simpler method is to use a sulfonic acid derivative of one
of the two components of the coupling reaction. Many azo
dyes are prepared by the coupling of phenols and amines with
diazotized sulfanilic acid.
Since sulfanilic acid in the form of the inner salt is not very
soluble in water, it is converted into the soluble sodium salt prior
to diazotization:
2H,N.C 6 H 4 .SO 3 + Xa 2 CO 3 >- 2H 2 N.C 6 Hi.SO 3 Na + CO 2 + H 2 O
— SOsNa
N
NaO3S—^ >—N = N — ^ /~ \
(Alkali-stable form)
the product, bring this all into solution by heating and stirring,
set the beaker in a pan of ice and water and let the solution
cool undisturbed.1 Eventually cool thoroughly by stirring and
collect the product on a Biichner funnel. Use saturated sodium
chloride solution, rather than water, for rinsing the material out
of the beaker and for washing the filter cake free from the dark-
colored mother liquor. The filtration is somewhat slow.2
The product dries only slowly and it contains about 20 per
cent of sodium chloride. The crude yield is thus not signifi-
cant and the material need not be dried before being purified.
This azo dye is too soluble to be crystallized from water; it
may be obtained in a fairly satisfactory form by adding satu-
rated sodium chloride solution to a hot, filtered solution of the
dye in water and cooling, but the best crystals are obtained
from aqueous alcohol. Transfer the filter cake to a beaker,
wash the material from the paper and funnel with water, and
bring the substance into solution at the boiling point. Avoid a
large excess of water but use enough to prevent separation of
solid during nitration (volume: about 100 cc). Filter by
suction through a Biichner funnel which has been preheated on
the steam bath (wash). Pour the filtrate into a beaker (wash),
estimate the volume and if this is greater than 120 cc. evaporate
by boiling. Cool to 80°, add 200-250 cc. of alcohol, and allow
crystallization to proceed. Cool well before collecting. Rinse
the beaker with mother liquor and wash finally with a little al-
cohol. The yield of pure, crystalline material is 13-16 g.
Orange II separates from aqueous alcohol with two molecules
of water of crystallization and allowance for this should be
made in calculating the percentage yield. When the water of
1
This gives a more easily filterable product. If time permits it is still better to
allow the solution to cool in the air.
2
If the filtration must be interrupted, close the rubber suction tubing while the
pump is still running with a screw pinch clamp placed close to the filter flask and
then disconnect the tubing from the pump. Fill the funnel and set the unit aside;
if the robber stopper fits properly the suction will be maintained and filtration will
continue. See the discussion on page 321 of the use of a rubber dam or balloon
in slow nitrations.
2IO EXPERIMENT 41
TESTS
1. Solubility and Color. — Compare the solubility in water
of Orange II and Methyl Orange and account for the difference
in terms of structure. Treat the first solution with alkali and
note the change in shade due to salt formation; to the other
solution alternately add acid and alkali.
2. Reduction. — Characteristic of an azo compound is the
ease with which the molecule is cleaved at the double bond by
the action of reducing agents to give two amines. Since the
amines are colorless, the reaction is easily followed by the color
change. The reaction is of use in the preparation of hydroxy-
amino and similar compounds, in the analysis of azo dyes by
AZO DYES 211
the nitric acid completely suspend the crude benzil in about ioo
cc. of water, heat until the solid melts, remove the flame and add
10 per cent sodium carbonate solution until it no longer pro-
duces an effervescence. The addition of the cold solution causes
the oil to solidify, and the material is again collected after some
stirring. The yellow lumps need be dried only superficially
before being crystallized from alcohol. Yield, 14-17 g.; m.p.
94-95°-
Properties. — Benzil forms yellow prisms melting at 95°.
It reacts with the usual ketone reagents such as phenylhydrazine
and the Grignard reagent, and as an a-diketone it exhibits certain
special reactions characteristic of this more limited group of
compounds. On treatment with alcoholic potassium hydroxide
it undergoes the benzilic acid rearrangement:
CeHs \X / OH
CeH6COCOC«Hs + KOH — > 7
C x/
C9H6 COOK
second hole in the stopper of this receiving flask insert the end
of a second condenser clamped in a vertical position. (The
arrangement is shown in Fig. 16, page 160.) The main con-
densation takes place in the receiving flask. The whole appa-
ratus must be ready for immediate use, with the cooling water
running and the ice in place, before mixing the reagents.
Disconnect the reaction flask and pour into it 240 cc. of
water and then 45 cc. of concentrated sulfuric acid, followed by
55 g. of hydroquinone. Mix these reagents well and then add
70 g. of powdered manganese dioxide, mix the contents quickly,
and at once connect the flask with the receiving system and
steam distil. The oxidation is a brisk reaction and the quinone
distils so rapidly at first that it may clog the tube of the first
condenser. Watch this tube and when it begins to fill, run
the water out of the condenser until the yellow solid is all melted.
The distillation requires from one-half to three-quarters of an
hour.
Push any material lodged in the two condensers into the re-
ceiver with a long rod, cool the distillate thoroughly and collect
the product. Spread it out on a paper until dry but no longer,
or material will be lost through sublimation.
The yield is 35-40 g. and the product usually requires no
further purification. Pure quinone melts at 1160 and darkens
when exposed to the light.
Toluquinone. — 0-Toluidine is the best starting material
available for the preparation of this homologue of quinone.
The yield is not good, but Clark's method of oxidation furnishes
a means of preparing the compound which in other respects is
quite satisfactory.
Procedure. — Follow in detail the above procedure for the
preparation of quinone, using the following quantities and re-
agents: 280 cc. of water, 45 cc. of concentrated sulfuric acid,
20 g. (20 cc.) of o-toluidine, 70 g. of manganese dioxide.
The yield is about 11 g. Toluquinone melts at 68-690 and
resembles quinone in most of its properties.
|ff-Naphthoquinone. — One of the most generally applicable
230 EXPERIMENT 46
CrO,
CH3
II
O Vitamin
A separation must be made from this substance, from unreacted
phytol and its dehydration product phytadiene, and from
unchanged starting hydroquinone. The latter is removed com-
pletely by extraction from ether with dilute alkali; the substi-
tuted hydroquinone with its long alkyl side chain is a cryptophe-
nol (hidden phenolic properties) and remains in the ether phase.
Since hydroquinones are very sensitive to air oxidation in the
presence of alkali, sodium hydrosulfite is added to keep the sub-
stances in the reduced form during the extraction operation.
When the material recovered from the ether layer is treated with
petroleum ether, the ketonic by-product, the phytol, and phy-
tadiene all dissolve readily, while the vitamin hydroquinone,
being phenolic, is less soluble in the hydrocarbon solvent and
separates as a solid. By suitable centrifugation and washing, it
QUINONES 237
paired tubes to the same point, cool well in ice and centrifuge.
Decant the brown supernatant liquor into the original tared flask,
fill the tubes with fresh solvent and stir the white sludge to an
even suspension, cool, centrifuge, and decant as before. Evap-
oration of the liquor and washings gives 1.1-1.3 g. of residual oil,
the difference giving an indication of the yield of vitamin to be
expected. Dissolve the portions of washed sludge of vitamin Ki
hydroquinone in a total of 10-15 cc - of absolute ether, and add a
little Norit for clarification if the solution is at all pink or dark.
Add 1 g. of silver oxide and 1 g. of magnesium sulfate. Shake for
20 minutes, filter into a tared flask, and evaporate the clear yellow
solution on the steam bath, removing traces of solvent at the
water pump. Undue exposure to light should be avoided when
the material is in the quinone form. The residue is a light yellow,
rather mobile oil consisting of pure vitamin Ki; yield 0.55-0.65 g.
To observe a characteristic color reaction, transfer a small bit
of vitamin on the end of a stirring rod to a test tube, stir with 1 cc.
of alcohol, and add 1 cc. of 10 per cent alcoholic potassium hy-
droxide solution; the end pigment responsible for the red color
is phthiocol. A sample for preservation is transferred with a
spatula, or with a dropper made by drawing out a piece of glass
tubing, into a small specimen vial which is sealed, labeled, and
wrapped in metal foil or black paper to exclude light.
Suction
into the boiling liquid through a glass tube drawn out to a fine
capillary and provided at the top with a section of suction tubing
which can be closed with a screw pinchcock which serves to
regulate the flow of air. The pinchcock is closed at the begin-
ning of the operation and carefully opened after the system has
been evacuated until there is a steady stream of bubbles. Some
further adjustment is required usually during the heating in
order to secure even boiling with a minimum amount of air.
The capillary should extend to the very bottom of the flask
and for the best results it should be slender and flexible so that
it will whip back and forth in the boiling liquid. Another method
of preventing bumping is to introduce sufficient glass wool into
the flask to fill a part of the space above the liquid.
To remove a fraction it is necessary to break the vacuum
242 VACUUM DISTILLATION
•Water
"Manometer
- Suction
Pump
To Drain
FIG. 23. — Vacuum Distillation Assembly
1
Adapter and receiver devices of improved design are described by Noonan,
Industrial and Engineering, Chemistry, Analytical Edition, 10, 34 (1938), Dunicz,
ibid., 11, 28 (1939), and Cloke, ibid., 12, 329 (1940).
246 VACUUM DISTILLATION
760 mm.
60
200'
1
For a modified design see Diels and Riley, Berichte ier deulschen chemischen
Gesellschaft, 48, 901 (1915).
DISTILLATION OF SOLIDS 253
liquid froths over into the receiving bulb the flask is tilted to
such a position that this bulb can drain through the connecting
tube back into the distillation bulb when suitably wanned.
At the end of the distillation the vacuum is broken by the
careful opening of the pinchcock and the contents of the receiving
bulb may be melted and poured out. This method of emptying
the bulb is sometimes inadvisable, however, because the hot,
molten material may be susceptible to air oxidation. In such a
case the material is allowed to solidify and cool completely before
breaking the vacuum. The solid is then chipped out with a clean
knife or with a strong nickel spatula and the last traces recovered
with the solvent to be used in the crystallization. The bad tar
usually remaining in the distillation bulb is best removed by
adding small quantities of concentrated nitric and sulfuric acids,
mixing the layers well, and heating the mixture while the flask
is supported by a clamp under the hood. After cooling and
pouring the acid mixture down the drain, loose char is removed
with water and a brush and the process is repeated.
EXPERIMENT 47 1
NAPHTHOL-AS
(Anilide of 2-Hydroxy-3-Naphthoic Acid)
OH
+ H2NC6H5 S
COOH
the solution under gentle suction (to avoid breaking the paper).
On acidifying the nitrate with hydrochloric acid the product
separates as a very fine precipitate and in order to facilitate
filtration it is well to digest the suspension close to the boiling
point for about 10 minutes. Filter hot and wash well with water.
If the product should be colored by a trace of green material
this impurity may be removed by extraction with hot alcohol,
in which the Naphthol-AS is only very slightly soluble. This
should be done before the product is dried by stirring it with
alcohol on the steam bath and filtering. Yield, 15-17 g.; m.p.,
244-246°.
The Naphthol-AS should be quite pure enough for the dyeing
experiment, but it will be of interest to try a few crystalliza-
tion tests. The following solvents should be tried, for they are
often of service in dealing with compounds sparingly soluble in
the usual organic solvents: nitrobenzene, s-tetrachloroethane
(CHC12CHC12).
The experiment can be varied by substituting for aniline other
common primary aromatic amines.
EXPERIMENT 48
DYES AND DYEING
In carrying out the following experiments keep in mind the
fact that considerable damage to the laboratory or the clothing
may result from careless work. It is entirely possible to avoid
staining the working space or the person and this is a case in
which neat manipulation will be clearly evident to the instructor.
Stirring rods are nearly as convenient as the fingers for manipu-
lating dyed cloth until it is thoroughly washed, and they are
more easily cleaned. In case of an accident see the note on
page 208.
Most cotton cloth available contains inorganic material in the
form of a filler or of sizing and this may have a mordanting
action which will obscure the true behavior of cellulose material
toward some of the dyestuffs. The cotton supplied for the
experiment should be freed of sizing by boiling it with soda
solution.1
Unless otherwise specified the small quantities of dyes and
reagents called for may be estimated, and it is better to use too
little material rather than too much.2
(1) Picric Acid. — (Direct to wool and silk.3) Dissolve 0.5 g.
of the acid in a little hot water to which a few drops of sulfuric
acid have been added. Heat pieces of wool, silk, and cotton in
this bath for one minute, then remove them with a stirring rod,
rinse well, wring, and dry. Describe the results.
(2) Congo Red, a Benzidine Dye. — Dissolve 0.1 g. of Congo
Red in 400 cc. of water, add about 1 cc. each of 10 per cent solu-
1
Boil for 2 hours with 2 per cent sodium carbonate solution, repeat with fresh
olution and wash thoroughly.
2
The dyes required are best supplied in individual waxed envelopes.
3
Picric acid stains on the skin can be removed by applying a coating of collodion
and, after 10 minutes, peeling this off with a knife blade.
257
258 EXPERIMENT 48
FORMATION OF DYESTUFFS
(1) Phenolphthalein. — Mix o.i g. of phthalic anhydride and
o.i g. of phenol in a test tube, add 2 drops of concentrated sul-
furic acid, and heat gently over a small flame with constant
agitation for about 2 minutes. The melt will become dark red
but should not blacken. When cool, treat with 5 cc. of water
and then add very gradually, with shaking, a dilute solution
of sodium hydroxide until a permanent pink color is obtained.
Then test the suitability of the material as an indicator by adding
first a trace of acid and then a trace of alkali.
(2) Fluorescein. — Heat gently for 2 minutes a mixture of
0.1 g. each of phthalic anhydride and resorcinol to which 3-4
drops of concentrated sulfuric acid have been added. Allow to
cool, add 5 cc. of water, make alkaline with sodium hydroxide.
Add a drop of this solution to a test tube full of water.
(3) Crystal Violet, a Triphenylmethane Dye. — Michler's
ketone has the structure of />,/>'-tetramethyldiamino-benzo-
phenone: (CH,),N.C,&.CO.C6H4.N(CH,)j. In the presence of
phosphorus oxychloride, aniline adds to this compound in such
a way that the para carbon of aniline becomes joined to the
carbon of the carbonyl group, while the para hydrogen becomes
attached to the oxygen. In the presence of an acid, here derived
from the phosphorus oxychloride, a dye is formed.
Place 0.1 g. of Michler's ketone, 5 drops of dimethyl aniline,
and 2 drops of phosphorus oxychloride in a test tube, and heat
the tube in boiling water for one-half hour. Add 10 cc. of water
and stir.
Add several drops of this solution to 20 cc. of water and treat
DYES AND DYEING 261
with a little ammonia. Let stand until the color has disappeared
and then add hydrochloric acid.
Write the formula for crystal violet and account for the color
changes noted.
If the original solution is allowed to stand over night, crystals
of crystal violet should separate.
EXPERIMENT 49
SULFANILAMIDE
The amide of an acid having no interfering groups can be
obtained by converting the acid to the acid chloride by means
of either phosphorus pentachloride or thionyl chloride and
treating the reaction product with ammonia. This direct proc-
ess cannot be used for the preparation of the amide of sulfanilic
acid unless the amino group is protected by acetylation against
attack by the halogenating agent. Since the amino group of
sulfanilic acid is not free but is bound in an inner salt or dipolar
ion structure, the substance must be converted into the sodium
salt prior to treatment with acetic anhydride. The salt, however,
is not soluble in acetic anhydride, and the reaction proceeds so
poorly that the preparation of />-acetaminobenzenesulfonyl
chloride by this method leaves much to be desired.
A much better route to this intermediate consists in the treat-
ment of acetanilide with excess chlorosulfonic acid. The sulfonyl
I>HCOCH3 NHCOCH 3
V
SO2C1
chloride group is thereby substituted into the para position and
the water formed reacts with more of the reagent to form sulfuric
and hydrochloric acids. ^-Acetaminobenzenesulfonyl chloride
(m.p. 148-1490) can be obtained in this way in excellent yield
and purity. (Chlorosulfonic acid is very corrosive to skin and
clothing and reacts with water with great violence; a graduate
used to measure the reagent should be drained thoroughly into
the reaction vessel and then cautiously held under the tap in a
slanting position.)
Conversion to the amide is accomplished conveniently by
262
SULFANILAMIDE 263
SO2C1 SO 2 NH 2 SO 2 NH 2
fanilamide goes into solution in the form of the hydrochloride,
H2NSO2C6H4NH3CI, and the free base is obtained by neutraliza-
tion with sodium bicarbonate.
Procedure. — The chlorosulfonation is conveniently carried
out without solvent in a 250-cc. Erlenmeyer flask fitted with a
stopper which is connected by means of a section of rubber tubing
to a gas trap (page 54) to entrain the liberated hydrogen chloride.
The reaction is more easily controlled when the acetanilide
employed is in the form of a hard cake than when it is in a
powdered condition. Place 10 g. of acetanilide in the flask, melt
it over a free flame, and cause the material to solidify over the
lower walls of the flask by swirling and cooling in an air blast.
Cool thoroughly in an ice bath, measure 25 cc. of chlorosulfonic
acid into a dry graduate, add the reagent all at once, and put in
place the stopper connected to the gas trap. The flask is now
removed from the ice bath and swirled until a part of the solid
has dissolved and the evolution of hydrogen chloride is proceed-
ing at a rapid rate. Occasional cooling in ice may be required to
prevent a too brisk reaction. In 5 to 10 minutes the reaction
subsides and only a few lumps of acetanilide remain undissolved.
When this point has been reached, heat the mixture on the steam
bath for 10 minutes to complete the reaction, cool the flask under
the tap, and pour the oily mixture slowly in a thin stream with
stirring into 150 cc. of ice water contained in a 600-cc. beaker
which is cooled in an ice bath (hood). Rinse the flask with cold
water and stir the precipitated />-acetaminobenzenesulfonyl
264 EXPERIMENT 40
PROCEDURE
(1) Note the color, odor, physical state, crystalline char-
acter. — Try to distinguish between a characteristic, pure color
and an " off " shade or tint which may be due to an impurity.
The samples available may contain traces of foreign coloring
matter and still be sufficiently pure for purposes of the tests.
Even the best grades of the liquid amines may become discolored
on storage, as your own experience with various grades of aniline
probably has shown, but the color is dull and not full-bodied.
Crystals are usually classified as needles, plates, or prisms,
but if they are too small for a recognition of the form the solid
is described as microcrystalline in order to distinguish it from
amorphous material.
(2) Examine the behavior on heating. — If the unknown is a
solid, heat a small sample carefully on a knife blade. If it melts
nicely, determine the melting point; if not, see if it leaves a
large residue of inorganic material when burned, indicating a
metal salt. (A slight residue is not significant; see page 9.)
THE IDENTIFICATION OF ORGANIC COMPOUNDS 271
CLASSIFICATION
GROUPS I AND II
NOTES
1. If the compound is not easily soluble in cold water, treat
it as a water-insoluble substance.
2. The addition of hydrochloric acid to a water solution of
the unknown may give a precipitate of a carboxylic acid (solid);
sodium hydroxide may precipitate an amine (oil or solid), partic-
ularly if the solution is concentrated or if solid sodium chloride
is added, or it may cause the liberation of ammonia (odor). In
either case the material (from a larger sample of the unknown)
should be collected (either by nitration or by extracting with
ether) and the carboxylic acid or the amine then can be studied
further as in IV A or III. The salt of a sulfonic acid is not
affected by adding hydrochloric acid. If such a salt is sus-
pected, it should be analyzed for sulfur. A sulfonic acid or its
salt often can be identified from the melting point of the p-tohii-
dine salt (prepared as on page 140).
274 EXPERIMENT 51
IV
SOLUBLE IN DIL. NaOH2
III A B
SOLUBLE IN DIL. HC1l
SOLUBLE IN NaHCCh INSOLUBLE IN NallCOa
NOTES
1. Use very dilute acid (2-3 drops of 10 per cent hydro-
chloric acid and 1-2 cc. of water). Some amines dissolve only
when the mixture is heated; if solution then occurs, neutralize
with alkali and see if this precipitates the amine. If a part of
the solid appears to dissolve, decant and neutralize the super-
natant liquor.
2. If the unknown is colored, be careful to distinguish between
the dissolving and the reading of the sample. Some quinones
(colored) react with alkali and give highly colored solutions. On
the other hand, some phenols (colorless) dissolve and then
become oxidized to give colored solutions. Some compounds
(e.g. benzamide) are hydrolyzed with such ease that careful obser-
vation is required to distinguish them from acidic substances.
3. A good test consists in making the ester, which is not
soluble in sodium hydroxide solution and which sometimes has a
characteristic odor. Cover about 0.2 g. with 2-3 cc. of methyl
alcohol, add 4 drops of concentrated sulfuric acid, and boil
5-10 minutes (steam bath). Cool, add 10 cc. of water, smell,
and see if the solid or oily precipitate fails to dissolve when the
cold mixture is made alkaline with sodium hydroxide. A better
conversion to the ester can be obtained by refluxing the mixture
THE IDENTIFICATION OF ORGANIC COMPOUNDS 275
GROUPS V AND VI
V VI
CARBONYL NEUTRAL NITROGEN
COMPOUNDS COMPOUNDS
A B C A B
NOTES
1. This is a general property of oxygen- and nitrogen-contain-
ing compounds and depends upon the formation of oxonium or
ammonium salts. The test gives a means of distinguishing such
inert compounds (not included here) as the phenol ethers, which
dissolve, from the hydrocarbons, which do not dissolve.
2. Test for the presence of nitrogen.
3. Quinones (colored) can be recognized by their easy reduc-
tion to hydroquinones (usually colorless). Suspend a small
sample in a little water, add a small pinch of sodium hydro-
sulfite (Na^Ci) and heat. A green quinhydrone is sometimes
observed as an intermediary product. The hydroquinone may
separate as a colorless solid or it may remain dissolved in the hot
solution. If an anthraquinone is suspected (high melting point,
slight solubility, slow reduction) add sodium hydroxide solution
along with the hydrosulfite and keep the solution alkaline. A
characteristic red vat will then develop if the quinone belongs
THE IDENTIFICATION OF ORGANIC COMPOUNDS 277
SO8H NO 2
NOj NHj
NH, /NHAc
_Ac2O
~NaAc
•NHj
NH JNHJ]
Hypothetical Amino-a-naphthoquinone
NH.
NH NH2
Hypothetical
O
OH
NH.C1 NHAc
V
minutes until most of the solid has dissolved, and then heat it
for just 15 minutes on the steam bath, stirring well at the start
in order to bring the remaining particles into solution. Toward
the end of the period specified the disulfonic acid should begin
to separate on the walls of the flask, particularly on scratching.
Cool well in an ice bath, dissolve the product in 25 cc. of water,
cool the solution and place it in a small dropping funnel. This
should be supported by a clamp in such a way that the solution
can be run into a 250-cc. beaker which is cooled in an ice bath.
Place 6 cc. of concentrated nitric acid (sp. gr. 1.42) in the beaker
and, while rotating this in the bath to effect good cooling, add the
solution of naphthol disulfonic acid by drops in the course of
about 10 minutes (1 drop per second until one-half is added,
then at twice this rate 1 ). When the addition is complete, warm
the mixture very gently on the steam bath in such a way that
the maximum temperature is reached only in about 5 minutes.
Stir well and watch for a vigorous reaction. After applying the
full heat for 5-10 minutes longer there should be no noticeable
increase in the amount of the yellow nitration product. Dilute
the mixture with several volumes of water, collect the crude
dinitronaphthol and wash it well with water.
Without drying the precipitate, wash it into a beaker and dis-
solve the crude material in 200 cc. of water containing 4 cc. of
concentrated ammonia solution (sp. gr. 0.90) at the boiling
point. Filter the hot solution by suction and add 10 g. of
ammonium chloride in order to salt out the ammonium salt
(Martius Yellow). Cool the mixture by stirring in an ice bath
and collect the precipitate. This should be washed with a solu-
tion containing about 1 per cent of ammonium chloride.
Save about 0.3 g. of the crude Martius Yellow for purification.
This sample may be precipitated again as the ammonium salt,
but it should eventually be converted to the free 2,4-dinitro-i-
naphthol (Compound I). This may be crystallized from alcohol;
m.p. 1380.
1
In working with larger quantities it is well to insert a thermometer and keep
the temperature below 10°.
MARTIUS YELLOW AXD ITS REDUCTION PRODUCTS 285
for reactions 3-5, the other for the series 6-8. The whole of the
solution may of course be used for either series (using double the
quantities of the reagents). In either event the solution should
be completely utilized as soon as possible. Notice that both
reactions 3 and 6 can be carried to a suitable stage within a few
minutes.
(3) Aminonaphthoquinone-imine (II). — To one half of the
acid solution of diaminonaphthol add 27 cc. of 1 N ferric chloride
solution, followed by 8 cc. of concentrated hydrochloric acid to
decrease the solubility of the red oxidation product (common
ion effect). The quinone-imine hydrochloride should begin to
crystallize within a few minutes on cooling the solution in an ice
bath and scratching the walls of the vessel very thoroughly with
a stirring rod.1 Collect the product and wash it with a small
quantity of 10 per cent hydrochloric acid (not water!). Yield,
about 2 g.
The material not required for use in Sections 4 and 5 should
be purified as follows: dissolve the sample by gentle warming
in a few cubic centimeters of water containing 2-3 drops of
concentrated hydrochloric acid, shake for a minute or two with
animal charcoal, filter by suction, add concentrated hydrochloric
acid to induce crystallization and cool in ice. Test the action of
alkali and of sodium hydrosulfite on aqueous solutions of the
substance.
(4) Aminonaphthoquinone-imine Diacetate (III). — A mix-
ture of 0.3 g. of the dry aminoquinone-imine, II, and 0.3 g. of
fused sodium acetate is treated in a test tube with 2 cc. of acetic
anhydride and the mixture is warmed gently (not above 8o°)
over the steam bath and stirred thoroughly until red particles
are no longer discernible. Acetylation is then complete. Pour
the mixture into a small beaker of water and stir until the excess
acetic anhydride has either dissolved or become hydrolyzed.
1
In order to induce crystallization most effectively the glass must be rubbed
until there is a visible scratch. The rubbing should be confined to one spot
and this should be slightly above the surface of the liquid, where there is a
liquid film.
MARTIUS YELLOW AND ITS REDUCTION PRODUCTS 287
NOTES
1. Reduction with Sodium Hydrosulfile. — In the early in-
vestigations of the reduction of Martius Yellow the reduction
was accomplished by the use of stannous chloride and the tin
was removed from the acid solution by displacement with
metallic zinc. The process, however, is both tedious and un-
certain, and the use of sodium hydrosulfite as the reducing agent
represents a great simplification of the method. Since this re-
agent is not soluble in the organic solvents and can be used only
in an aqueous medium, it is evident that it is a distinct advantage
that the dinitro compound which is to be reduced is an acidic
substance and forms water-soluble salts. The ammonium salt
is more soluble than the alkali metal salts and is better suited
for the reaction. The experiment shows that the reduction is
very rapid and easily carried out.
It is also possible, if somewhat less convenient, to reduce di-
nitronaphthol itself, rather than the salt, with sodium hydrosul-
fite. In this case it is best to suspend the yellow solid in alcohol
and to add an aqueous solution of the reducing agent at the boil-
ing point. The same procedure is recommended for the reduc-
tion of other compounds which are not appreciably soluble in
water, while the simpler method described above serves well in
the alternate case, or where the substance can be obtained as a
salt.
Sodium hydrosulfite serves as a convenient reagent for the
reduction of many other nitro compounds as well as azo com-
pounds (page 210) and quinones (page 238).
2. Acetylation in aqueous solution. — An amine is always more
easily acetylated than a phenol of similar structure, and if an
aminophenol is treated in the dry condition with acetic anhy-
dride the amino group is the first to be attacked. It is not
easy, however, to stop the reaction at this stage and the pure
iV-acetate is not readily prepared by this method. A much
better method is to conduct the acetylation in aqueous solution
(see page 164). The amino group again reacts very rapidly to
2O.O E X P E R I M E N T 52
These works, which are of much the same character but which
cover somewhat different subjects, give exhaustive discussions of
the various standard operations of the organic laboratory, and of
the methods and procedures used for carrying out reactions of a
great many different types. Their greatest value lies in the
systematic organization of the literature, but they often further
provide authoritative suggestions and opinions. Books of more
modest proportions but more modern are those of Bernhauer,
"Einfiihrung in die organisch-chemische Laboratoriumstechnik "
(1934), Morton, "Laboratory Technique in Organic Chemistry"
(1938), and Weygand, " Organisch-Chemische Experimentier-
kunst" (1938).
"Organic Syntheses" is in a different category, since it is an
annual publication giving tested directions for the preparation
of various compounds. The first nine volumes were combined,
revised, provided with extensive references, and published as a
Collective Volume in 1932. The procedures not only are of use
for the preparation of specific compounds, but they also serve
as models for the adaptation of a known reaction to a new case.
Too much emphasis cannot be placed on the necessity for
consulting the original literature. "Beilstein" and the other
secondary sources mentioned serve an admirable purpose, but
they in no sense supplant the original papers to which they
furnish so convenient a guide. One who is satisfied with books
of reference alone will miss many points of interest and im-
portance in the writings of the investigators. It is impossible
RUBBER STAMPS 297
to include all material of value in a secondary source and there
is a wealth of forgotten ideas and suggestive concepts to be
unearthed by anyone who will study with diligence both the
early and the recent literature of organic chemistry.
BENZENE-RING STAMPS
Satisfactory hexagons can be cut from rubber stoppers by
the following method, and after a little practice it is possible to
make stamps of different styles for rings varying from 3 mm.
to 20 mm. in height. The small stamps are useful in labelling
specimen tubes, the large ones in preparing reports and manu-
scripts. The cutting is done with razor blades, and a particu-
larly sharp blade is reserved for the finer work. A hard (usually
old) rubber is preferred both because it is more easily cut than
a soft, elastic rubber and because it gives a stamp of firmer edge.
On the small end of the stopper two parallel cuts, lines 1 and
2 in Fig. 29a, are first made by placing the razor edge flat on the
surface of the rubber and slowly drawing the blade back and
forth with steady pressure. After each line has been cut to a
depth of 2-3 mm. the stopper is cut away roughly with an older
blade in the manner shown in Fig. 29J to give a tapered slice.
The distance between cuts 1 and 2 determines the dimension
indicated, and the symmetry of the final ring is largely de-
pendent upon the accuracy with which the cuts are made parallel
in this and in the following operations.
The next two parallel cuts, 3 and 4, are made at a suitable
angle to the first two and care must be taken to make the distance
298 THE ANALYTICAL SAMPLE
between the cuts exactly the same as that between cuts 1 and 2.
Cuts s and 6 are then made; they should be equidistant from
and parallel to the long axis of the ring, and the distance between
them determines the width of the hexagon. The stopper is then
cut away on all sides.
To clear out the inside of the hexagon and leave an outline,
make cuts about 1 mm. deep in the positions indicated by the
lines of Fig. 29c, working the rubber carefully with a sharp blade.
The cut in each corner of the ring usually does not show in
the completed stamp and it greatly facilitates the sharp cutting
of the outline and the removal of the center. The edges should
be about 0.5 mm. wide. The rubber in the center is carefully
cut away by folding back each edge, laying the razor flat and
cutting horizontally at a depth of 1 mm. A feature of the
construction is that with the long taper the edges are open to
view when the stamp is in use, thus facilitating a proper align-
ment.
Cott
longer than may appear necessary. After the glue has dried,
coat the label with a suitable lacquer such as vinylite, collodion,
or paraffin; rub off the excess material with a towel while it is
still soft.
For a discussion of the characterization of a new compound
see pages 282-283.
Samples which are to be sent through the mails can be packed
securely in a block of wood with holes bored to accommodate the
specimen tubes. A piece of cotton introduced either at the
bottom of the hole or on top of the cork or screw cap will hold
this in place and prevent the tube from rattling; the hole is
closed with a cork or with the dowel arrangement shown in
Fig. 32. The block can be labelled and stamped, or inclosed in a
tnanila envelope.
CHAPTER II
APPARATUS AND METHODS
Equipment for the Laboratory Bench. — In addition to an
adequate supply of the usual pieces of apparatus, the following
items of equipment may be desirable:
Bottle or tube (stoppered) of chips of porous plate
Closed tube or box for melting point capillaries. The capillary
can be cut twice the required length, sealed at both ends,
and stored in this form; a cut in the middle then gives two
tubes. Some substances give more sharply defined and
higher melting points in Pyrex capillaries than in soft glass,
and it may be desirable to evacuate and seal the tube.
Fine capillary tubes can be cut most readily with the sharp
edge of a piece of unglazed clay plate.
Scissors, knife
Glycerol bottle with a glass rod inserted through the stopper
(lubricating rubber tubing and stoppers, boring rubber
stoppers, lubricating the bearing of a mechanical stirrer)
Acetone (for drying apparatus, washing out tars)
Decolorizing carbon (e.g., Norit, Darco)
Spatulas: small one of silver or platinum for analytical
weighing; 18-cm. silver spatula (page 27); 25-cm. nickel
spatula; flat, "pressing" spatula of nickel or of Allegheny
metal
Dropping tubes
Test solutions in small bottles provided with droppers mounted
in screw cap tops: dilute solutions (distilled water!) of
sodium hydroxide, sodium carbonate, sodium bicarbonate,
and hydrochloric acid; concentrated sulfuric acid (all-glass
container)
Rack for graduates of various sizes (inverted; best over the
sink)
303
3°4 EQUIPMENT FOR THE BENXH
Tin Foil
Asbestos
Ball
Bearings
(Precision ground)
Stainless __
Steel Bands •Platinum
Wire
Support
Pyrex
Baking Dish
1i Pyrex Dish
pressure equalizing tube connect-
ing the two arms; with this ar-
rangement there is little escape of
fumes and the liquid level remains
the same in both arms. The ap-
paratus is mounted in a Pyrex dish
to catch the acid in case of break-
Is Iron Rod age The Anschiitz thermometers
Fio. S3--Thermometer Rack a r e conveniently mounted when
not in use in a wire rack with provision for drainage (Fig. 53).
Melting Point Blocks. — A metal block apparatus is useful
for the determination of melting points above 3000. The block
4
A simplified method of winding the heating element is as follows. Two \*
strips of asbestos paper are wetted and stuck to the upper and lower walls of the
curved part of the tube, leaving the side walls bare. The resistance wire is attached
at one end to a stainless steel strap and wound over the partly dried asbestos strips
with TV' spacings. When the lower end of the curve is reached, the winding is
covered with a spiral of asbestos tape for insulation and the wire is returned in
three or four turns to the second binding post. The wiring is then wrapped with a
thin layer of asbestos paper, and this is moistened and worked into a smooth,
adherent covering.
ALUMINUM BLOCK 329
Dry Air
Rubber
Stopper
CHROMATOGRAPHIC ADSORPTION
The selectivity with which even closely related substances are
adsorbed from solution on the active surface of certain finely
divided solids affords the basis for a
very effective method of separating
mixtures. When a solution containing
a mixture of pigments is passed slowly
through a column packed with a white
adsorbent such as alumina, the indi-
/Filter Paper vidual constituents tend to be retained
^Porcelain Plate in different colored zones, the most
^Rubber Disk strongly adsorbed pigments being held
at the top of the column and the ones
having less affinity for the adsorbent
appearing at lower levels. Although
the initial separation of the different
colored layers may not be very dis-
tinct, the zones often become much
more sharply differentiated on filtering
through the column a fresh portion of
FIG. 62. — Modified Skau the original solvent or a quantity of a
Tube second solvent. This operation con-
stitutes the development of the chromatogram. The process
of development is continued until the zones are spread over the
entire length of the column. When the operation is conducted
in a tower of the type shown in Fig. 63, the variegated col-
umn can be pushed carefully out of the open end of the tube
with a plunger onto a clean paper. It is then cut into sections
with a knife or spatula and each highly pigmented zone is eluted
separately with a solvent capable of stripping the colored sub-
stance from the adsorbent, the pigment being obtained by fil-
tration and evaporation.
SEPARATION OF PIGMENTS 337
The effectiveness of the separation is strikingly demonstrated
by passing an extract from a few green leaves through a tower
packed with layers of alumina (bottom), calcium carbonate, and
powdered sugar; the developed chromatogram is resolved into
zones of chlorophyll b (top), chlorophyll a, xanthophyll, and
carotene.1 In general an organic compound is adsorbed most
strongly from a solution in a nonpolar solvent such as hexane
or benzene and is but loosely held when
the adsorbent is in contact with alcohol,
or other polar solvent, for this itself has
a strong affinity for the active surface of
the solid and tends to displace the much
less plentiful pigment present. There-
fore hexane is an effective solvent for
: —Adsorbent
the preparation and development of the
chromatogram, and alcohol, or benzene Paper
containing a little alcohol, serves well for Porcelain Plate
the elution. Blotter
The chromatographic method was dis-
covered by the botanist Tswett and here-
tofore the most prominent applications
have been in the investigation of plant
pigments. The method, however, can be
employed extensively in various simplified FIG. 63 — Adsorption Col-
and convenient forms in many problems umn, Suction Filtration
of general laboratory practice, and the following notes apply
particularly to the more general uses of the adsorption procedure.
A substance does not have to be very highly colored to give a
distinctly visible adsorption band, particularly since the adsorb-
ate may be a complex of accentuated color and also because
the material retained in a section of the column is in a concen-
trated form. A pale yellow reaction product may be resolvable
by adsorption analysis into a yellow component and a colorless
one, or it may be found that the slight color is due to a trace of
1
Zechmeister and Cholnoky, "Die Chromatographische Adsorptionsmethode,"
J. Springer, Vienna, 1937.
338 SELECTIVE ADSORPTION
GLASS BLOWING 1
By E. B. Hershberg
Types of Glass. — Laboratory tubing made of soft glass
(soda-lime glass) softens at a comparatively low temperature
(400-4500) and can be worked most satisfactorily using an air-
gas blast lamp with a quiet blue flame just tipped with yellow.
With soft glass, simple practice operations can be carried out
in the flame of a Bunsen burner; a microburner of the type
shown in Fig. 51 (page 326) is useful for learning the technique
of joining pieces of 6-8 mm. tubing. Soft glass has a high
coefficient of expansion and must be brought to the working
temperature slowly in a yellow flame in order to avoid cracking;
the temperature during working should not be too high or the
surface may become frosted as the result of volatilization of
alkali. After the blowing operation has been completed, the
glass should be annealed, in order to relieve strains, by rotating
13
A convenient method for the purification of anthracene in quantity consists
in distilling a mixture of 50 g. of the crude hydrocarbon and 700 cc. of ethylene
glycol from a i-l. distilling flask directly (without a condenser) into a second flask
which is cooled when required with a stream of water. The distillation is continued
until about 50 cc. of residue is left, and the mixture of anthracene and ethylene
glycol in the receiver is redistilled as before. With a good grade of crude anthra-
cene, blue-fluorescent material is obtained on two distillations in 70-80 per cent
yield. — Communicated by W. W. Hartman, Eastman Kodak Co.; see Yule,
U. S. Patent 2,213,755 (1940).
1
Reference books:
Frary, Taylor and Edwards, "Laboratory Glass Blowing," McGraw-Hill
Book Co., New York (1928).
Morey, "The Properties of Glass," Reinhold Publishing Corp., New York
(1938).
Vigreux, "Le soufflage du verre," Dunod, Paris (1930).
Woytacek, "Lehrbuch der Glasblaserei," J. Springer, Vienna (1932).
Useful pamphlets giving instructions for blowing Pyrex glass are distributed
by the Corning Glass Works.
346 FLAMES
right angles to the tube in order to lead the crack around the
circumference.
Flaring of Glass Tubing. — A simple flaring tool is made
from a 4" X i" X f" charcoal block by cutting it at one end to
a smooth, uniform conical point, using a grinding wheel or a
knife and sandpaper. Untreated charcoal does not tend to
stick to glass as does a triangular metal reamer or an arc-
light carbon rod, both of which must be rubbed while hot into
beeswax prior to use. Charcoal is too fragile to be used for
flaring tubes of small diameter and in this case carbon rods are
preferable.
In forming a flare, the tube, stoppered or sealed at one end, is
rotated in an oblique position in a rather narrow flame which
impinges on both the front and the back edge at the same time
without heating much of the body of the tube. When the glass
is sufficiently plastic the tube is removed from the flame and the
charcoal reamer is pressed lightly into the opening and rotated
with sufficient pressure to turn out the edge. A reinforcing rim,
such as that shown on the Pyrex pressure vial of Fig. 43, page
317, can be formed by reheating the flare in exactly the same
manner until the turned edge flows together into a rim, when the
reamer is again applied. The process is repeated enough times
to give a beaded edge of the desired thickness.
Bends. — For the production of a successful bend it is im-
portant to apply heat uniformly to the entire section of tubing
necessary for the bend. As in all comparable manipulations, the
tube is grasped in the left hand with the palm down, and in the
right hand with the palm up, for these positions make it possible
to swing the right-hand end of the tube into a position for blowing
without interruption of the steady process of synchronized rota-
tion of the two ends. The rotating is best done in the direction
in which the top of the tubing moves away from the body.
Facility in the rotation of the two ends at exactly the same
rate is gained only with careful practice; in the beginning stages
it may be helpful to make a chalk mark on each side of the heated
portion in order to indicate the proper alignment. If a U-bend
BENDS 349
a b e d e
FIG. 65. - Blowing a Round End
together on the same axis and then pulled slightly to reduce the
thick ring of glass at the joint. (With Pyrex glass these opera-
tions are performed without complete removal of the tube from
the flame.) The flame is adjusted quickly to a narrow point
and the tube is rotated in such a way as to heat only the welded
section and cause it to shrink in diameter and increase in wall
thickness. The tube is withdrawn and blown, without pulling,
until the heated section is expanded slightly beyond the normal
diameter. The bulbous part is heated in a softer flame and
gently pulled enough to reduce the diameter of the seal to that
of the tube. In order to secure the correct wall thickness it may
be necessary to reheat the seal and repeat the shrinking and
enlarging operations.
3
Tapered corks useful for stoppering small tubes are available in the following
sub-sizes (below No. 1): o, 00, 00J, 000, 000^.
T-SEALS 351
Tubes of unequal size can be joined by drawing out the larger
tube, cutting it at a point where the diameter corresponds to that
of the smaller tube, and making the seal essentially as described
above. Another method is to make a round end on the larger
tube, heat the central spot on the bottom with a sharp flame,
and blow out a bulb of fragile glass which is brushed off with a
file until a flared opening remains of diameter corresponding to
that of the tube to be joined. By the same method, capillary
0 Q Q Q Q
A A A A A
Vn
Vn
Vn Vo V
a
a
b e d e
Fio. 66. — Construction of a T-Seal
tubing can be provided with a flared opening suitable for making
a seal to a piece of ordinary tubing of the same diameter.
T-Seals. — The tube which is to form the straight part of the
joint is sealed or stoppered at one end and a small spot in the
middle is heated with a sharp flame (Fig. 66a) and blown out so
as to form a bulge (b) of diameter somewhat less than that of the
tube which is to be sealed at this point. The bulge is heated
carefully at its tip and blown out to a thin-walled bulb (c). The
thin glass is brushed away with a file until a short side tube is
left which can be joined to the second tube by the method
described above for making a straight seal (d and e).
Bulbs. — Small flasks suitable for microdistillations can be
blown from Pyrex tubing as follows. The tube is sealed at the
-352 BULBS
n
c d
FIG. 68. — Construction of a Condenser with a Ring Seal
SOLVENTS
Absolute Alcohol (b.p. 78.40). — The complete dehydration
of the constant-boiling mixture which ethyl alcohol forms with
water and which contains 95.6 per cent alcohol by weight is best
accomplished in two steps. The bulk of the water can be re-
moved conveniently in the laboratory by the reaction with quick-
lime, but this gives at best a product containing about 99.5 per
cent of alcohol and the small trace of water may interfere
seriously in some reactions and operations. Commercial grades
of absolute alcohol likewise may contain traces of water, for
pure alcohol is extremely hygroscopic and easily picks up mois-
ture during transfer or storage. (The industrial method consists
in the distillation of the azeotropic mixture: alcohol, water,
benzene. A mixture of all three components distils first, then
benzene and alcohol, then absolute alcohol.) Of the many
methods which have been suggested for the removal of the last
traces of water the two outlined below appear to be the simplest
and most reliable.
Alcohol of approximately 99.5 per cent purity is prepared as
follows: A round-bottomed flask is charged about two thirds
full with 95 per cent alcohol and (fresh) quicklime broken into
lumps, using enough lime so that the pieces project above the
surface of the alcohol. A reflux condenser equipped with a
calcium chloride tube is attached and the mixture is refluxed
gently for about 1 hour and then allowed to stand for 2 or 3 days,
when the lumps should have largely disintegrated to a powder.
The alcohol is then refluxed for 1 hour and distilled into a suction
flask fitted by means of an adapter and protected with a calcium
chloride tube against the entrance of moisture. The distillation
is rather slow and considerable alcohol is retained by the solid
residue.
For the further dehydration of this material or of commercial
absolute alcohol a method has been developed by Smith 1 which
1
/ . Chem. Soc, 1288 (1927).
ABSOLUTE ALCOHOL 359
DRYING AGENTS
The common drying agents are listed below together with some
of the considerations which are of importance in the selection
of one which will be suitable for a given purpose.
Calcium Chloride: large capacity for the absorption of water
(forms the hexahydrate below 300), not very efficient, particu-
larly useful for preliminary drying. Usually unsuitable for dry-
ing: alcohols and amines (forms molecular compounds), phenols,
esters, acids (contains lime).
Potassium Hydroxide (solid): very efficient and rapid, but
limited almost entirely to use with amines.
Sodium (wire): very efficient but of use only with inactive,
neutral compounds (ethers, saturated and aromatic hydrocar-
bons) . The liquid or solution should be dried first with calcium
chloride to remove the bulk of the water.
Caution: Every precaution must be taken in using sodium
for drying purposes or as a reagent, for on no account must the
19
Scott, Walker and Hansley, / . Am. Chem. Soc, 58, 2442 (1936).
DRYING AGENTS 371
ALKYLATING AGENTS
Alkyl Iodides. — Methyl and ethyl iodide deteriorate rapidly
with the liberation of iodine if exposed to the light, and com-
mercial preparations which have been kept long in storage are
often found to be quite dark and unsuitable for use. Such
material can be purified, however, by shaking it with successive
portions of a dilute solution of either sodium thiosulfate or
sodium bisulfite until the color is completely bleached, washing
with water, drying over calcium chloride, and distilling the
product. The colorless distillate should be stored in a brown
bottle and kept out of the direct sunlight. As a further pro-
2
Hammond and Withrow, Ind. Eng. Chem., 25, 653, 1112 (1933).
3
Obermiller and Goertz, Z. physik. Chem., 109, 162 (1924).
4
Adkins and Rainey, "Organic Syntheses," 20, 9 (1940).
ALKYL IIALIDES 373
though not dangerously so. They should be kept off the skin
and manipulated under the hood. They are of particular serv-
ice for the alkylation of phenols and react only with difficulty
with the more strongly acidic carboxylic acids. The alcoholic
groups of a sugar can also be alky la ted by this method. To
convert a phenol into the methyl ether it is dissolved in a slight
excess of warm alkali, dimethyl sulfate is added, and the mixture
is heated on the steam bath and shaken or stirred mechanically.
When the solution becomes acid to litmus more alkali is added,
followed by a little dimethyl sulfate. The reagents are added
alternately, allowing the solution to become acid frequently,
until eventually no phenol precipitates on acidifying a test portion
of the alkaline solution. An alternate method is to add the al-
kali slowly to a stirred mixture of the phenol and dimethyl sul-
fate.
Higher alkyl sulfates are likewise good alkylating agents, but
they cannot be prepared satisfactorily by heating the alkyl
sulfuric acid, as in the case of the methyl and ethyl derivatives.
A method described by Barkenbus and Owen 2 involves the prep-
aration of the corresponding alkyl sulfite as an intermediate.
The process is generally applicable to the preparation of the
neutral normal primary alkyl sulfates, regardless of the length
of the carbon chain. The materials required are: the appropriate
alcohol, sulfuryl chloride, and thionyl chloride.
Alkyl ^-Toluene Sulfonates, ^-CHsCeKsSOaOR. — Esters of
this type may be obtained by the reaction of an alcohol with
^-toluenesulfonyl chloride.3 The esters are useful for certain
alkylations and have been found to give good results where more
usual reagents present certain difficulties.4
Diazomethane is an invaluable reagent for the methylation of
carboxylic acids or other substances which are strongly or
moderately acidic. It is a yellow gas and is ordinarily employed
2
/ . Am. Chem. Soc, 56, 1204 (1934); Suter and Gcrhart, "Organic Syntheses,"
19, 27, 29 (1939).
3
Roos, Gilman and Beaber, "Organic Syntheses," Coll. Vol. I, 139 (1932);
Sekera and Marvel, / . Am. Chem. Soc, 55, 345 (1933).
4
Kanevska, Arch. Pharm., 271, 462 (1933).
DIAZOMETHANE 375
dry and undiluted. The liquid is not required for ordinary work,
however, and the gas can be handled with safety by diluting
it with nitrogen. However it is prepared, diazomethane is best
dissolved at once in ether, for the ethereal solution is entirely
safe and this is the most convenient form in which to employ the
reagent. The ethereal solution if anhydrous can be kept for a
day or two, but it undergoes gradual decomposition with the
liberation of gas; the containing vessel must not be stoppered
tightly but should be protected with a calcium chloride tube and
kept in a cold place. It is well to prepare fresh reagent when
required and to use it at once. Diazomethane is poisonous, but
with reasonable care no difficulty should be experienced in
handling an occasional small quantity. In work requiring the
continued use of the reagent there is danger of developing a
supersensitivity to attacks of asthma and fever. Special care
must also be taken in handling nitrosomethylurethane (see be-
low).
Several good methods have been described for the preparation
of diazomethane and the choice depends somewhat upon the
availability and current prices of the starting materials. The
method listed below as i(a) is.perhaps the simplest when only
small quantities are required and when the presence of methyl
alcohol and moisture in the ethereal solution is not objectionable;
methods i(b) and 2 yield an absolute ethereal solution of the
reagent. In some cases, as in ordinary methylatkms, methyl
alcohol acts as a catalyst, and where two or more modes of
reaction are possible the presence or absence of this catalyst may
control the course taken. Method 4 is applicable to the prepara-
tion of higher diazohydrocarbons.
1. From Nitrosomethylurethane, CH3N(NO)COOC2H5 (also
called Ethyl Nitrosomethylcarbamate). — The conversion of
this substance into diazomethane by the action of a potassium
alcoholate may be represented as follows:
KOR , . / N
CH 3 NCOOC 2 H 6 >• CH 3 N[COOJH >- CH a N > C H 2N' II + H 2 O
I I" I II N
NO NO <—I HO-N
DIAZOM ETHANE 377
The yield is good (65 per cent) and this is an excellent method
for the preparation of a dry solution of the reagent in pure ether.
Full details of the procedure, together with directions for
the preparation of nitrosomethylurea starting with ammonia,
methylamine, or acetamide are given by Arndt.9 About
90 g. of methylurea nitrate is required to produce 10 g. of diazo-
methane.
3. From Hydrazine and Chloroform. — In the presence of
alcoholic potassium hydroxide solution these reagents combine
in the following manner:
9
Arndt and Amende, Z. angew. Chem., 43,444 (1930); Arndt and Scholz, ibid.,
46, 47 (1933); Arndt, "Organic Syntheses," 15, 3 (1935).
DIAZOMETHANE 379
ACYLATING AGENTS
Acetic Anhydride (b.p. 136.40). — The reagent often deterio-
rates as the result of improper storage and it is well to test it
either in a preliminary, small-scale run or by shaking a sample
with ice-water and rapidly titrating the free acetic acid. A satis-
factory purification can be effected by careful fractionation, and
if the material is of a practical grade it is well to distil it first
from fused sodium acetate in order to eliminate halogen com-
pounds and metals.
Acetyl Chloride (b.p. 510). — Student preparations of this
reagent are likely to contain free hydrogen chloride and low-
boiling esters containing phosphorus. After a preliminary dis-
tillation, in case it is very crude, the material is mixed with
about one tenth its volume of dimethyianiline and fractionated.
This removes both types of impurities and gives a clear product
which will not react with sodium.
Benzoyl Chloride (b.p. 1970). — See page 194.
Benzenesulfonyl Chloride (m.p. 14.50, b.p. i2O°/io mm.).—
Three methods of preparation are described in "Organic Syn-
theses." 1 Benzenesulfonyl chloride solidifies at 13-140; impure
material should be distilled at the water pump.
^-Toluenesulfonyl Chloride (m.p. 690, b.p. i46 o /i5 mm.).—
The crude (technical) material can be purified by dissolving it
in benzene, shaking the solution with dilute alkali, drying it over
potassium carbonate, removing the solvent, and distilling the
product at the pressure of the water pump.
Other Acid Chlorides. — Probably the most generally applica-
ble method of converting an acid into the acid chloride is by
treatment with phosphorus tri- or pentachloride (page 76).
Thionyl chloride (page 76) sometimes proves to be a slightly
more convenient reagent, particularly when the product can be
distilled, but in some instances it gives rise to side reactions. It
is difficult to remove traces of thionyl chloride from a nonvolatile
acid chloride, and the material retained may cause difficulties
1
"Organic Syntheses," Coll. Vol. I, 77 (1932).
THIONYL CHLORIDE
OTHER REAGENTS
Thionyl Chloride (b.p. 770). — Commercial preparations of
this reagent often contain traces of acids and other impurities
INORGANIC GASES
Ammonia. — The gas may be obtained from a cylinder of
liquid ammonia or generated in the apparatus shown in Fig. 72.
Concentrated ammonia water (sp. gr. 0.89) is heated in a with
a very small flame at first and then more strongly and the gas
evolved is dried in a tower of soda lime (b). A trap (c) is in-
troduced just before the flask (d) in which the ammonia is to be
22
I. G. Farbcnind., English Patent 303,375 (1930); French Patent 636,06s
(1928); Swiss Patent 131,959 (1929); Gruene, U. S. Patent 1,759,111 (1930);
Fieser, / . Am. Chem. Soc, 53, 3546 (1931); Fieser and Peters, ibid., 64,3742, 4347
(1932); Fieser and Fieser, ibid., 55, 3342 (1933).
23
Fieser and Hershberg, / . Am. Chem. Soc, 60, 1658 (1938).
«• Zahn and Ochwat, Ann., 462, 81 (1928).
25
Norris and Klemka, / . Am. Chem. Soc, 62, 1432 (1940).
CARBON DIOXIDE 391
absorbed in the reaction mixture or in a solvent, and the tubes
are so arranged that any liquid sucked back into the trap will
eventually find its way again into the absorption vessel.
Carbon Dioxide. — Gaseous carbon dioxide suitable for some
purposes but containing air may be obtained from a cylinder of
the liquid material or by the evaporation of dry ice from a
bottle wrapped with a towel and fitted with a stopper carrying
a gas outlet and a Bunsen valve for the release of excess pressure.
The gas also may be generated by dropping hydrochloric acid
(1 : 1) onto lumps of marble, as shown in Fig. 73, or, where
small amounts of gas are required over a long period, with the
use of a Kipp, Ostwald, or other standard form of generator.
For use in the Dumas method for the determination of nitrogen,
where traces of air are objectionable, the marble is boiled with
water before use or replaced by either potassium carbonate or
sodium bicarbonate. A convenient dry ice generator suitable
392 CARBON MONOXIDE. CHLORINE
until about half of it has been added; when the gas evolution
begins to slacken the mixture in the generating flask is heated
with a small flame at first and then nearly to boiling in order to
complete the reaction. For each gram of potassium perman-
ganate 6.2 cc. of concentrated hydrochloric acid is used (excess),
and the theoretical yield is 1.12 g. of chlorine. The actual yield
does not fall far short of this amount and the recovery is prac-
tically quantitative if the chlorine is swept out of the flask and
bottles with a stream of carbon dioxide.
Hydrogen Bromide. — Gaseous hydrogen bromide may be
prepared by dropping bromine into boiling tetralin,3 but the
removal of traces of bromine and of hydrocarbon from the gas
stream is rather troublesome. A better method is by the direct
combination of the elements. Claisen and Eisleb 4 heated bro-
mine to a temperature of about 400, where the vapor pressure
is 0.5 atmosphere, and passed in a stream of hydrogen. The
gas mixture issuing from the flask contained approximately
equimolecular quantities of the two elements, and combination
was effected by passing the mixture through a hot tube packed
with platinized quartz or asbestos. Any excess bromine was
removed in a tube charged with beads moistened with red
phosphorus. The method has been improved by Ruhoff, Bur-
nett and Reid,5 whose description should be consulted for details.
These authors find the catalyst to be unnecessary and simply
pack the combustion tube with clay chips and heat it with the
full force of a burner. Excessive bromine is removed in a tube
filled with copper turnings. According to Ionescu and Radu-
lescu,6 pure dry hydrogen bromide can be prepared in 80-90 per
cent yield by dropping bromine onto petroleum ether in the
presence of aluminum bromide.
Hydrogen Chloride. — Hydrogen chloride is available in cylin-
ders. Small quantities of the gas are conveniently generated by
dropping concentrated sulfuric acid onto sodium chloride covered
3
Houben, "Methoden d. org. Chem.," 3rd Ed., I l l , 1156.
4
Ann., 401, 28 (1913).
5
"Organic Syntheses," 16, 35 (1935).
6
Bid. soc. chem. Romania, 17, 309 (1935).
394 HYDROGEN CHLORIDE
sulfuric acid is run into the large separatory funnel and the
concentrated hydrochloric acid is placed in the dropping funnel
and run in when required through the long stem. Entering in
this way at the bottom of the layer of heavier liquid, the hy-
drochloric acid becomes thoroughly mixed with it. The capillary
construction permits the stem to remain filled with liquid so that
the flow is continuous. The connection between the gas exit
and the top of the dropping funnel serves to equalize the pressure
HYDROGEN CHLORIDE. NITROGEN 395
ACYLATION
Acetylation with acetic anhydride is sometimes accomplished
by reftuxing the hydroxy or amino compound for an extended
period with an excess of acetic anhydride, but the more usual
practice is to take advantage of the marked catalytic influence
exerted by a trace of either sulfuric acid or a basic reagent such
as sodium acetate or pyridine. The addition of a few drops of
concentrated sulfuric acid to a suspension of the substance in
acetic anhydride at room temperature usually initiates a reac-
tion, as evidenced by a marked temperature rise, and the material
may all go into solution without application of heat and then
separate in the form of the acetate (example: acetylsalicylic
acid, page 222). . Acetylations often can be initiated similarly
with pyridine. Sodium acetate functions less spectacularly be-
cause it does not dissolve readily in cold acetic anhydride; in
this case the mixture is warmed for a time on the steam bath or
heated at the reflux temperature. Acetic anhydride is such an
effective solvent for acetylated compounds that it is usually
best to decompose the excess reagent with water even though
some of the product has separated from the mixture in a crystal-
line condition. The mixture can be poured into a large volume
of water and stirred until the oily anhydride has disappeared,
although with a large batch this may take several hours. With
any but a highly sensitive acetyl derivative the following rapid
method of decomposition is often satisfactory. The acetylation
mixture is boiled steadily under a reflux condenser and water is
added cautiously by drops through the condenser. Although
the hydrolysis is exothermic, the reaction proceeds rapidly but
without turbulence when steady boiling is deliberately main-
397
398 ACETIC ANHYDRIDE IN AQUEOUS SOLUTION
Mercury Valve
(to react with the Mg(OH)X), and the excess acid titrated with
standard sodium hydroxide solution, using methyl orange as
the indicator.
For determining when a Grignard compound has been com-
pletely consumed, as when gaseous formaldehyde is passed into
the ethereal solution, Gilman's test 7 for the presence of the
Grignard reagent is useful: about 0.5 cc. of the ethereal solution
is pipetted and treated with an equal volume of a 1 per cent solu-
tion of Michler's ketone in dry benzene, and then, slowly, with
1 cc. of water. The addition of several drops of a 0.2 per cent
solution of iodine in glacial acetic acid then produces a charac-
teristic greenish blue color if Grignard reagent has been present.
The Reaction Proper. — The usual, or direct, reaction is one
in which a given component of a synthesis is caused to react as
completely as possible with a Grignard reagent, and the ordinary
procedure is to prepare a slight excess of the reagent as described
above and to stir this under reflux in the original apparatus while
slowly adding a solution of the second component in ether.
Some addition reactions, however, do not proceed satisfactorily
at the boiling point of ether and require forcing conditions, that
is, a more elevated temperature. The desired conditions are
obtained by preparing a solution of the Grignard reagent in
ether, adding a dry hydrocarbon solvent of higher boiling point,
and removing the bulk of the ether by distillation. By using
benzene, toluene, or xylene for displacing the ether the tempera-
ture obtainable in the subsequent reaction can be varied over a
considerable range. Air should be excluded with nitrogen dur-
ing the operation, for oxidation may occur rapidly at the high
temperatures. It is sometimes desirable to dispense entirely
with the use of diethyl ether in order to facilitate the isolation
of a reaction product boiling in the same range as this solvent.
In the preparation of w-pentane, b.p. 35.50, Noller 8 used di-n-
butyl ether, b.p. 1410, as the solvent.
7
Gilman and Schulze, / . Am. Chem. Soc, 47, 2002 (1925); Gilman and Heck,
ibid., 52, 4949 (1930).
8
"Organic Syntheses," 11, 84 (1931).
INVERSE REACTIONS 409
Sodium.
Na + CsHsOH
(a) «-C4H5CN • «-C 4 H 9 CH 2 NH s u
«-Amylamine
Na + GftOH
(b) «-C4H9COOC2H6 • K-C4H9CH2OH »
«-Amyl alcohol
Na+CHuOH
(c) /5-Naphthylamine >• a<;-Tetrahydro-/S-naphthylamine12
Tin-Mercury Couple.
HCl
Benzoin Desoxybenzoin
Copper-Zinc Couple.14
Cu-Zn
RX >-RH
alcohol
6
Levene, "Organic Syntheses," 15, 27 (1935).
7
Kamm, "Organic Syntheses," Coll. Vol. I, 435 (1932).
8
Kuhn, "Organic Syntheses," 13, 74 (1933).
9
Clar, Ber., 72, 1645 (i939)-
10
Kuhn and Winterstein, Ber., 65, 1737 (1932).
11
Adams and Marvel, / . Am. Chem. Soc, 42, 310 (1920).
12
Waser and Mollering, "Organic Syntheses," Coll. Vol. I, 486 (1932).
13
Ballard and Dehn, / . Am. Chem. Soc, 54, 3970 (1932).
14
Preparation: Houben, 3rd Ed., II, 304 (1925).
REDUCING AGENTS 417
Aluminum Amalgam.1
COCOOR Ai-Hg CHOHCOOR16
C H a C O O R moist ether C H 2 C O O R
Oxalacetic ester Malic ester
Magnesium-Magnesium Iodide.17
Mg - Mgl2
(CHS)SCO • (C 6 H 6 )2C C(C 6 H5) 2
(H*O) ]
] I
OH OH
to remove the solvent and traces of mesityl oxide and other odor-
iferous condensation products of acetone which may be present.
The yields usually are excellent, and the Meerwein-Ponndorf
method of reduction has the great advantage of being specific
for the carbonyl group and without influence on other centers of
unsaturation, as illustrated in the following examples:
AI(OCaH7) 3
CH3CH = CHCHO >- CHsCH = CHCH 2 OH 48
Crotonaldehydc Crotyl alcohol (85-90% yield)
OXIDATION
Potassium Permanganate. Mandelic acid >• phenylgly-
oxylic acid > benzoic acid (page 217).
Sodium Dichromate. Ethyl alcohol > acetaldehyde (page
80).
OXIDIZING AGENTS 429
Anhyd. NajSOT7^
Diphenyldiazomethane
Similar oxidations have been conducted with the addition of
anhydrous calcium sulfate to absorb the water formed.9
Lead Dioxide, PbO2,10 is used for the oxidation of the leuko
bases of triphenylmethane dyes.
Potassium Ferricyanide. — This is a mild oxidizing agent
which sometimes attacks a side chain (slowly) without affect-
ing the aromatic ring, thus: u
CH, COOH
KiFe(CN).
NaOH '
HOOC
(The reaction is useful for structure determination but is hardly
of preparative value.)
Oxides of Nitrogen (N2O3, NO2) etc.). — The preparation of
the gas from arsenious oxide and nitric acid and its use in the
following oxidation:
CH2(COOC2H6)2 >- CO(COOC2H5)2
Ethyl oxomalonate
are described in detail by Dox.12
7
Ber., 37, 4744 (1904).
8
Staudinger, Anthes and Pfenninger, Ber., 49, 1932 (1916).
9
L. I. Smith and Hoehn, "Organic Syntheses," 20, 47 (1940).
w
Preparation: Gattermann-Wieland, "Methods," p. 325 (1937).
11
Weissgerber and Kruber, Ber., 52, 352 (1919); Ruzicka and co-workers,
Helv. Chim. Ada, 9, 976 (1926); 14, 238 (1931).
12
"Organic Syntheses," Coll. Vol. I, 261 (1932).
HYPOCHLORITE 43I
(a) (b)
second type (b) has been isolated from the reaction with 0-amino-
benzaldehyde.24
When applied to substances sparingly soluble in aqueous alkali,
the reaction is best conducted by adding perhydrol and con-
centrated alkali to a solution of the material in pyridine; ex-
ample: 3-phenanthrol-4-aldehyde > morphol.26
Hydrogen Peroxide — Acetic Acid. — One use for the reagent
is in the hydroxylation of an olefinic compound to the corre-
sponding glycol. The reaction may be conducted at room
temperature over a period of several days.27 An improved pro-
cedure 28 consists in heating a mixture of acetic acid and 30 per
22
Fieser, Campbell, Fry and Gates, / . Am. Chem. Soc, 61, 3216 (1939); Tishler,
Fieser and Wendler, ibid., 62, 2866 (7940).
23
Dakin, Am. Chem. J., 42, 477 (1909).
24
Bamberger, Ber., 36, 2042 (1903).
25
v. Wacek and Eppinger, Ber., 73, 644 (1940).
26
Barger, J. Chem. Soc, 113, 218 (1918).
27
Hilditch, / . Chem. Soc, 1828 (1926).
28
Scanlan and Swern, / . Am. Chem. Soc, 62, 2305, 2309 (1940).
434 HYDROGEN PEROXIDE WITH CATALYSTS
J
H3C NO H3Cl NO2
tageously applied to methylated compounds, for more drastic
methods result in some attack of the alkyl substituents.
Perbenzoic Acid (Benzoyl Hydrogen Peroxide), C6H5COOOH.
The preparation of the reagent has been described by various
investigators.33 An illustration of its special function is in the
preparation of styrene oxide 34 (Prileschajew reaction):
C6H5CII = CH2 + C6H6COOOH > C 6 H 6 CH-CH 2 + C6H6COOH
\ /
39
Diphenic acid is obtained in 70 per cent yield by refluxing 50 g. of phenan-
threnequinone in 150 cc. of acetic acid with 500 cc. of 6 per cent hydrogen peroxide
for 3 hours; Linstead and Waipole, / . Chem. Soc, 855 (1939).
30
Arnold and Larson, / . Org. Chem., 5, 250 (1940).
31
Milas and Sussman, / . Am. Chem. Soc, 58, 1302 (1936).
32
Kuhn and van Klaveren, Ber., 71, 779 (1938).
33
Tiffeneau, "Organic Syntheses," Coll. Vol. T, 422 (1932); Braun, ibid., 13,
86 (1933); Brooks and Brooks,/. Am. Chem. Soc, 55, 4309 (1933). For observa-
tions concerning the stability of different preparations of perbenzoic acid, see
Calderwood and Lane, / . Phys. Chem., 45, 108 (1941).
34
Hibbert and Burt, "Organic Syntheses," Coll. Vol. I, 481 (1932).
PERACIDS. SELENIUM DIOXIDE 435
between 550 and 8o°. At the end of the reaction the thick and
somewhat dark solution is cooled and the crystalline lead tetra-
acetate which separates is collected and washed with acetic acid.
The crude product without being dried is dissolved in hot acetic
acid and the solution is clarified with Norit, filtered, and cooled.
The colorless crystalline product is dried in a vacuum desiccator
over potassium hydroxide and stored in the desiccator; yield
320-350 g.
Procedure 2:41 A 5-liter three-necked flask fitted with a
mechanical stirrer (tantalum wire or glass, no seal required), a
thermometer, and a 10-mm. gas inlet tube is charged with 2500 cc.
of glacial acetic acid and 700 cc. of acetic anhydride and the
mixture is warmed to 6o° on the steam bath (hood). Dry
chlorine gas is passed into the solution with stirring and 700 g.
of dry red lead powder is added in 15-20 g. portions, each addi-
tion being made only after the color due to the previous portion
has faded. The temperature is maintained at 60-750 throughout
the addition, which takes about 2 hours. When the reaction is
complete, 1-2 g. of Norit is added to the hot mixture containing
precipitated lead chloride and the suspension (at 750) is filtered
rapidly by suction using a large preheated Biichner funnel.
The residue consisting largely of lead chloride is extracted by
digesting it with 100 cc. of warm acetic acid, filtering, and
repeating the process with two successive 100-cc. portions of
solvent. The combined filtrates on cooling deposit the lead
tetraacetate in colorless needles, and the product is collected,
dried in a vacuum desiccator, and stored out of contact with
moist air; yield 500-550 g. This material is found by titra-
tion to be 94-95 per cent pure; it contains a small amount
of lead chloride but is entirely satisfactory for most purposes.
A purer product can be obtained by recrystallization, but the
process is attended with considerable loss. Distillation of the
filtrate gives acetic acid satisfactory for use in another prepara-
tion.
41
Procedure of Oesper and Deasy, / . Am. Cliem. Soc, 61, 972 (1939), with slight
modifications.
438 GLYCOL CLEAVAGE
—C-OH
I + Pb(OAc)4 >- + Pb(OAc)2 + 2H0Ac
—C-OH CO
I
tion. The reaction has been extended to a-keto acids and a-keto
alcohols by operating in a solution containing water or meth-
anol; u the hydroxylic component adds to the carbonyl group
to give a pseudoglycol, which then undergoes quantitative oxida-
42
Hockett and McClenahan, J. Am. Chem. Soc, 61, 1670 (1939).
43
Criegee, Kraft and Rank, Ann., 607, 159 (1933).
44
Bacr. / . Am. Chem. Soc, 62, 1597 (1940).
ACETOXYLATION 439
RC-C=O + H20
O OH
Another use of lead tetraacetate is in the acetoxylation of
compounds having a reactive hydrogen atom. Malonic ester
may be converted into acetyltartronic ester,46 CH2(CO2C2Ho)2
[5)2, and acenaphthene is attacked
in the ace-ring and gives 7-acenaphthenyl acetate in good yield.47
When such an oxidation is to be conducted in acetic acid solution
on a large scale, it often is convenient to dispense with the
preparation of lead tetraacetate and simply add red lead in
portions to an acetic acid solution of the compound to be
oxidized.47'48 Certain uniquely reactive hydrocarbons such as
3,4-benzpyrene can be acetoxylated in excellent yield by inter-
action with lead tetraacetate at a low temperature.49 Anthra-
cene affords o-acetoxyanthracene in moderate yield50 as the
result of an addition to the diene system.51
Both open-chain and cyclic unsaturated hydrocarbons are
susceptible to attack by lead tetraacetate. Usually the chief
reaction consists in the introduction of an acetoxyl group on a
carbon atom adjacent to the center of unsaturation, but since
addition to the unsaturated system may also occur a complex
mixture of products often results. Ketones can be acetoxylated
in the a-position with moderate success with lead tetraacetate.
Another use for the reagent is in the preparation of quinones
of very high potential. Diphenoquinone separates in a crystalline
46
McClenahan and Hockett, J. Am. Chem. Soc, 60, 2061 (1938); Hockettand
McClenahan, ibid., 61, 1667 (1939).
46
Dimroth and Schweizer, Ser., 56, 1375 (1923); Bak, Ann., 637, 291 (1938).
47
Fieser and Cason, J. Am. Chem. Soc, 62, 434 (1940).
48
Ward, / . Am. Chem. Soc, 60, 325 (1938); Scanlan and Swern, ibid., 62, 2305
(1940).
49
Fieser a n d H e r s h b e r g , J. Am. Chem. Soc, 6 0 , 1893, 2542 (1938).
60
K. H. Meyer, Ann., 379, 73 (1911).
61
Observation of S. T. Putnam.
44O PERIODIC ACID
OSO2OK
OH
k
HC1
> + HOSQiOK
I
OH
Gentisaldehyde
(cris)2c=o ^ = ^ = r - ^ \ c = o + (CII3)2CHOH
CATALYTIC HYDROGENATION
The methods available for the hydrogenation of organic com-
pounds may be classified as follows according to the nature of the
catalyst and the conditions employed for promoting the reaction:
(1) liquid phase, noble-metal catalyst (Pt, Pd), low temperature
(25-600), pressures slightly above one atmosphere (Willstatter);
(2) vapor phase, base-metal catalyst (Ni), high temperature
(3000), atmospheric pressure (Sabatier); (3) liquid phase, base-
metal catalyst (Ni, Cu-Cr), moderate temperature (150-2000),
high pressure (Ipatiev).
The low temperature method is very generally useful in ordinary
laboratory work, and a particularly satisfactory type of catalyst
and a serviceable form of apparatus were developed by Adams
and co-workers and are described in detail in "Organic Syn-
theses." 1 A bottle or a long-necked flask often serves as a satis-
factory vessel in which to conduct the hydrogenation. A flask
73
Reichstein and Euw, Ueh. Chim. Ada, 23, 136 (1940).
71
Inhoffen, Logemann, Hohlvveg and Serini, Bar., 71, 1032 (1938).
75
Kuwada and Joyama, / . Pharm. Soc. Japan, 57, 247 (1937) [Chem. Zentr., 2,
1612 (1938)].
1
Preparation of Adams platinum oxide catalyst: Adams, Voorhees and Shriner,
"Organic Syntheses," Coll. Vol. I, 452 (1932); apparatus for hydrogenation at
2-3 atm. pressure: ibid., p. 53.
HYDROGENATION FLASKS 447
having certain special features of design is shown in Fig. 77
(Hershberg; see note 16, page 451). Hydrogen is admitted
through a flexible brass spiral connected to the flask by means of
a two-way glass trap which prevents
Soldered
possible contamination with the metal Copper Tube
and which can be cleaned by means of
the capped side opening. The flask is Brass Inner.
provided with a sealed-in coil which Joint
can be used for heating the reaction Glass
mixture with hot water or steam or for
Capped
cooling it with tap water or with brine Cleaning
circulated by a small pump. The tube Compression Outlet
suspended from the rubber stopper is
provided with a series of baffles to
prevent the splashing of liquid into
the hydrogen inlet and to aid in the
washing down of any catalyst or solid
organic substance which tends to lodge
in the neck of the flask. The same
baffle construction is employed in the
flask shown in Fig. 78; this all-glass
unit is designed for use in special cases
where it is considered desirable to
avoid contact of the reaction mixture
with rubber. The baffling is made
by cutting staggered] -fa" slots in the
wide glass tube with a grinding wheel FIG 77. — Hydrogenation
and heating the glass above each cut Flask with Coil for Heat-
until it draws in. ing or Cooling
Certain useful modifications have been introduced in the pro-
cedure for the preparation of Adams platinum oxide catalyst,
which consisted originally in fusing chloroplatinic acid with
sodium nitrate in a casserole over a free flame at 500-550°. Cook
and Linstead 2 found that fusion with potassium nitrate gave a
somewhat more active catalyst. The temperature of the melt
2
J. Client, Soc.s 952 (1934).
448 ADAMS CATALYST
8
J Soc Chem Ind , 55, 14T (1936)
4
"Organic Syntheses," 17, 98 (1937)
5
Wichers, J Am. Chem Soc, 43, 1268 (1921); Baldeschwieler and Mikeska,
ibid., 57, 977 (1935)
PALLADIUM CATALYST 449
DEHYDROGENATION
The principal methods available for effecting the dehydro-
genation of hydroaromatic compounds consist in heating the
substance in question with sulfur, selenium, or palladium char-
coal, aromatization being attended with the formation of hy-
drogen sulfide, hydrogen selenide, or elementary hydrogen.
Sulfur acts more rapidly than selenium, it is effective at a lower
temperature, and it is less prone to give rise to the pyrolytic
cleavage of alkyl substituents from reactive positions.1 On the
other hand sulfur, by virtue of its great reactivity, may give rise
to troublesome side reactions or even yield a sulfur-containing
compound as the chief product.2 The less reactive selenium re-
quires a higher temperature and a longer reaction period but has
less tendency to combine with the organic material 3 and some-
times is found to operate very smoothly and cleanly. The
reaction temperature is so high, however, that the aromatiza-
tion may be attended with the loss or migration of alkyl groups
and the elimination or alteration of other substituents.4 Cata-
82
Certain polynuclear hydrocarbons are sufficiently reactive to undergo ready
partial hydrogenation over copper. I'henanthrene can be converted smoothly to
the 9,10-dihydride at low temperatures, and the remaining, isolated benzenoid
rings are attacked only slowly: Burger and Mosettig, J. Am. Chem. Soc, 58, 1857
(1936); Durland and Adkins, ibid., 69, 135 (1937); 60, 1501 (1938); Fieser and
Johnson, ibid., 61, 168 (1939).
1
Fieser and Hershberg, / . Am. Chem. Soc, 59, 1028, 2331 (1937); Fieser and
R. N. Jones, ibid., 60, 1940 (1938).
1
Fieser, / . Am. Chem. Soc, 55, 4977 (1933).
3
A by-product containing selenium, however, was encountered by Ruzicka,
Helv. Chim. Ada, 19, 419 (1936), in the dehydrogenation o£ /rarcs-(3-decalone.
4
For a discussion of normal and abnormal dehydrogenations, see Linstead,
"Annual Reports of the Chemical Society," 33, 294-312 (1936).
DEHYDROGENATION WITH SULFUR 455
7 mm. J
O.D. ' Bubbler Tube
230 mm. long overall
Guard
6mm.
Tube
fitted with wing tops furnish heat for the combustion. Asbestos
sheets are used at the ends of the combustion tube to diminish
the diffusion of heat. When the combustion is to be conducted
on a wooden bench the burners are mounted on a large piece of
asbestos board raised about one inch from the bench on wooden
runners.
The Absorption Train. — This consists of tubes for the ab-
sorption of water (E) and carbon dioxide (F), a guard tube (G),
and an aspirator bottle (H). Tube E is filled with Dehydrite
held in place by plugs of cotton, and tube F is similarly filled
with Ascarite and a terminal i-cm. layer of Dehydrite. The
ground glass joints are wiped and carefully sealed with stop-
cock grease.3 The Ascarite tube can be used until about one
third of the filling has been exhausted, as indicated clearly by
the color change (about 25 analyses). The Dehydrite tube
should be refilled when about a i-cm. layer of the solid becomes
noticeably mushy (about 50 analyses).
Absorption tube E is attached to the combustion tube with
the lubricated joint away from the source of heat. For con-
venience in handling, tube F is attached in the opposite position,
and it is connected in turn to the guard tube (G). These con-
nections are made by means of one-inch pieces of heavy walled
rubber tubing ( | by \ inch), which is prepared by rubbing out
the sulfur, moistening with glycerol and wiping dry. The ends
of the glass tubes should meet inside the rubber connections.
The absorption tubes are conveniently supported by hooks of
aluminum wire suspended from a straight piece of glass rod held
in a clamp on a ringstand. Caps are provided for the ends of
the absorption tubes made from short lengths of rubber tubing
cleaned and treated with glycerol as above and plugged with
short sections of glass rod.
3
The grease may be replaced by a glass cement made by melting together one
part of white wax and four parts of colophony resin. (Pregl, loc. cit., p. 35.) The
cement is applied to the warmed joint and the excess is removed mechanically and
by wiping with a cloth moistened with benzene. The tube is opened by warming
the joint and after it has cooled the contents can be removed and replaced without
disturbance of the hardened cement.
SEMIMICROANALYSIS 471
PROCEDURE
Burning Out the Combustion Tube. — The absorption train
is attached, the three Bunsen burners with wing tops are lighted,
and a slow stream of oxygen is passed through the tube; the
pressure regulator and the aspirator bottle are adjusted to main-
tain a constant slight pressure in the apparatus, with excess
oxygen bubbling out slowly around the pressure regulator. A
new tube should be burned out for a day or more and then tested
by making a blank determination in which the regular procedure
given below is followed in all details except for the use of a sample.
The carbon dioxide tube should remain practically constant in
weight, but the water tube gains about o.i mg. for every 300 cc.
of oxygen passed through. Correction is not made for this,
however, since the error seems to be partially compensated in
the actual combustion. For an old tube the burning out re-
quires from one-half to one hour, depending on the length of
time the tube has been standing unused.
When the combustion tube has been burned out sufficiently
the absorption tubes are disconnected and capped and a cap is
placed over the tip of the combustion tube. The stream of
oxygen need not be stopped; the gas may be allowed to escape
at the pressure regulator. The burner nearest the bubble
counter is turned off and the others are adjusted to allow the
rear part of the tube to cool while the filling is kept warm.
SEMIMICROANALYSIS 473